Epigenomic profiling reveals the somatic promoter landscape of primary gastric adenocarcinoma

ABSTRACT

The present invention relates to a method for determining the presence or absence of at least one promoter in a cancerous biological sample relative to a non-cancerous biological sample. The present invention also relates to a method for determining the prognosis of cancer in a subject, a method for modulating the activity of at least one cancer-associated promoter in a cell, a method for modulating the immune response of a subject to cancer, a method for determining the presence of at least one cancer-associated promoter in a cancerous biological sample relative to a non-cancerous biological sample and a biomarker for detecting cancer in a subject.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of priority of Singapore application No. 10201601142V, filed 16 Feb. 2016, the contents of it being hereby incorporated by reference in its entirety for all purposes.

FIELD OF THE INVENTION

The invention relates to a method for determining the presence or absence of at least one promoter in a cancerous biological sample relative to a non-cancerous biological sample.

BACKGROUND OF THE INVENTION

Gastric cancer (GC) is the third leading cause of global cancer mortality with high prevalence in many East Asian countries. GC patients often present with late-stage disease, and clinical management remains challenging as exemplified by several recent negative Phase II and Phase III clinical trials. At the molecular level, studies have identified characteristic gene mutations, copy number alterations, gene fusions, and transcriptional patterns in GC. However, few of these have been clinically translated into targeted therapies, with the exception of HER2-positive GC and traztuzumab. There is thus a strong need for additional and more comprehensive explorations of GC, as these may highlight new biomarkers for disease detection, predicting patient prognosis or responses to therapy, as well as new therapeutic modalities.

Promoter elements are cis-regulatory elements which function to link gene transcription initiation to upstream regulatory stimuli, integrating inputs from diverse signaling pathways. Promoters represent an important reservoir of biological, functional, and regulatory diversity, as current estimates suggest that 30-50% of genes in the human genome are associated with multiple promoters, which can be selectively activated as a function of developmental lineage and cellular state. Differential usage of alternative promoters causes the generation of distinct 5′ untranslated regions (5′ UTRs) and first exons in transcripts, which in turn can influence mRNA expression levels, translational efficiencies, and generation of different protein isoforms through gain and loss of 5′ coding domains. To date, promoter alterations in cancer have been largely studied on a gene-by-gene basis, and very little is known about the global extent of promoter-level diversity in GC and other solid malignancies.

Accordingly, there is a need for a method of profiling promoter elements in cancer.

SUMMARY

In one aspect there is provided a method for determining the presence or absence of at least one promoter in a cancerous biological sample relative to a non-cancerous biological sample, comprising: contacting the cancerous biological sample with at least one antibody specific for histone modifications H3K4me3 and H3K4me1; isolating nucleic acid from the cancerous biological sample having a signal ratio of H3K4me3 relative to H3K4me1 greater than 1, wherein the isolated nucleic acid comprises at least one region specific to said histone modifications; detecting a signal intensity of H3K4me3 in the isolated nucleic acid; and determining the presence or absence of at least one promoter in the cancerous biological sample based on the change in the signal intensity of H3K4me3 relative to the signal intensity of H3K4me3 in a non-cancerous biological sample.

In another aspect there is provided a method for determining the prognosis of cancer in a subject, comprising, contacting a cancerous biological sample obtained from the subject with at least one antibody specific for histone modification H3K4me3 and H3K4me1; isolating nucleic acid from the cancerous biological sample having a signal ratio of H3K4me3 relative to H3K4me1 greater than 1, wherein the isolated nucleic acid comprises at least one region specific to said histone modifications; detecting a signal intensity of H3K4me3 in the isolated nucleic acid; and determining the presence or absence of at least one cancer-associated promoter in the cancerous biological sample based on the change in the signal intensity of H3K4me3 relative to the signal intensity of H3K4me3 in a reference nucleic acid sequence, wherein the presence or absence of the at least one cancer-associated promoter in the cancerous biological sample is indicative of the prognosis of the cancer in the subject.

In another aspect there is provided a biomarker for detecting cancer in a subject, the biomarker comprising at least one promoter having a change in signal intensity of H3K4me3 in a cancerous biological sample relative to a non-cancerous biological sample.

In another aspect there is provided a method for modulating the activity of at least one cancer-associated promoter in a cell, comprising administering an inhibitor of EZH2 to the cell.

In another aspect there is provided a method for modulating the immune response of a subject to cancer, comprising administering to the subject an inhibitor of EZH2, wherein the EZH2 is associated with at least one cancer-associated promoter in the subject.

In another aspect there is provided a method for determining the presence or absence of at least one cancer-associated promoter in a cancerous biological sample relative to a non-cancerous biological sample, comprising: contacting the cancerous biological sample with at least one antibody specific for histone modifications H3K4me3 and H3K4me1; isolating nucleic acid from the cancerous biological sample having a signal ratio of H3K4me3 relative to H3K4me1 greater than 1, wherein the isolated nucleic acid comprises at least one region specific to said histone modifications; detecting a signal intensity of H3K4me3 in the isolated nucleic acid at a read depth of 20M; and determining the presence or absence of at least one cancer-associated promoter in the cancerous biological sample based on the change in the signal intensity of H3K4me3 relative to the signal intensity of H3K4me3 in a non-cancerous biological sample.

In one aspect, there is provided a biomarker comprising at least one promoter having a change in signal intensity of H3K4me3 in a cancerous biological sample relative to a non-cancerous biological sample for use in detecting cancer in a subject.

In one aspect, there is provided a use of a biomarker comprising at least one promoter having a change in signal intensity of H3K4me3 in a cancerous biological sample relative to a non-cancerous biological sample in the manufacture of a medicament for detecting cancer in a subject.

In one aspect, there is provided an inhibitor of EZH2 for use in modulating the activity of at least one cancer-associated promoter in a cell.

In one aspect, there is provided a use of an inhibitor of EZH2 in the manufacture of a medicament for modulating the activity of at least one cancer-associated promoter in a cell.

In one aspect, there is provided an inhibitor of EZH2 for use in modulating the immune response of a subject to cancer, wherein the EZH2 is associated with at least one cancer-associated promoter in the subject.

In one aspect, there is provided a use of an inhibitor of EZH2 in the manufacture of a medicament for modulating the immune response of a subject to cancer, wherein the EZH2 is associated with at least one cancer-associated promoter in the subject.

Definitions

The following are some definitions that may be helpful in understanding the description of the present invention. These are intended as general definitions and should in no way limit the scope of the present invention to those terms alone, but are put forth for a better understanding of the following description.

As used herein, the term “promoter” is intended to refer to a region of DNA that initiates transcription of a particular gene.

As used herein, the term “cancerous” relates to being affected by or showing abnormalities characteristic of cancer.

As used herein, the term “biological sample” refers to a sample of tissue or cells from a patient that has been obtained from, removed or isolated from the patient. The term “obtained or derived from” as used herein is meant to be used inclusively. That is, it is intended to encompass any nucleotide sequence directly isolated from a biological sample or any nucleotide sequence derived from the sample.

As used herein, the term “antibody” or “antibodies” as used herein refers to molecules with an immunoglobulin-like domain and includes antigen binding fragments, monoclonal, recombinant, polyclonal, chimeric, fully human, humanised, bispecific and heteroconjugate antibodies; a single variable domain, single chain Fv, a domain antibody, immunologically effective fragments and diabodies.

The term “specifically binds” as used throughout the present specification in relation to antigen binding proteins means that the antigen binding protein binds to a target epitope on an antigen with a greater affinity than that which results when bound to a non-target epitope. In certain embodiments, specific binding refers to binding to a target with an affinity that is at least 10, 50, 100, 250, 500, or 1000 times greater than the affinity for a non-target epitope. For example, binding affinity may be as measured by routine methods, e.g., by competition ELISA or by measurement of Kd with BIACORE™, KINEXA™ or PROTEON™.

As used herein, the term “isolated” relates to a biological component (such as a nucleic acid molecule, protein or organelle) that has been substantially separated or purified away from other biological components in the cell of the organism in which the component naturally occurs, i.e., other chromosomal and extra-chromosomal DNA and RNA, proteins and organelles. Nucleic acids and proteins that have been “isolated” include nucleic acids and proteins purified by standard purification methods. The term also embraces nucleic acids and proteins prepared by recombinant expression in a host cell as well as chemically synthesized nucleic acids.

As used herein, the term “nucleic acid” refers to a deoxyribonucleotide or ribonucleotide polymer in either single, or double stranded form, and unless otherwise limited, encompassing known analogues of natural nucleotides that hybridize to nucleic acids in a manner similar to naturally occurring nucleotides, “Nucleotide” includes, but is not limited to, a monomer that includes a base linked to a sugar, such as a pyrimidine, purine or synthetic analogs thereof, or a base linked to an amino acid, as in a peptide nucleic acid (MA). A nucleotide is one monomer in a polynucleotide. A nucleotide sequence refers to the sequence of bases in a polynucleotide.

As used herein, the term “prognosis” or grammatical variants thereof, as used herein refers to a prediction of the probable course and outcome of a clinical condition or disease. A prognosis of a patient is usually made by evaluating factors or symptoms of a disease that are indicative of a favorable or unfavorable course or outcome of the disease. The term “prognosis” does not refer to the ability to predict the course or outcome of a condition with 100% accuracy. Instead, the term “prognosis” refers to an increased probability that a certain course or outcome will occur; that is, that a course or outcome is more likely to occur in a patient exhibiting a given condition, when compared to those individuals not exhibiting the condition.

As used herein, the term “modulating” is intended to refer to an adjustment of the immune response to a desired level.

As used herein, the term “annotated promoter” refers to a promoter mapping close (<500 bp) to a known Gencode transcription start site (TSS).

The term “unannotated promoter” refers to a promoter mapping to genomic regions devoid of known Gencode TSSs.

As used herein, the term “canonical” in the context of a promoter refers to a promoter region exhibiting unaltered H3K4me3 peaks.

As used herein, the term “detectable label” or “reporter” refers to a detectable marker or reporter molecules, which can be attached to nucleic acids. Typical labels include fluorophores, radioactive isotopes, ligands, chemiluminescent agents, metal sols and colloids, and enzymes. Methods for labeling and guidance in the choice of labels useful for various purposes are discussed, e.g., in Sambrook et al., in Molecular Cloning: A Laboratory Manual, Cold Spring Harbor Laboratory Press (1989) and Ausubel et al., in Current Protocols in Molecular Biology, Greene Publishing Associates and Wiley-Intersciences (1987),

As used herein, the term “hypomethylated” refers to a decrease in the normal methylation level of DNA,

As used herein, the term “hypermethylated” refers to an increase in the normal methylation level of DNA.

As used herein, the term “about”, in the context of concentrations of components of the formulations, typically means +/−5% of the stated value, more typically +/−4% of the stated value, more typically +/−3% of the stated value, more typically, +/−2% of the stated value, even more typically +/−1% of the stated value, and even more typically +/−0.5% of the stated value.

Throughout this disclosure, certain embodiments may be disclosed in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the disclosed ranges. Accordingly, the description of a range should be considered to have specifically disclosed all the possible sub-ranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed sub-ranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.

Certain embodiments may also be described broadly and generically herein. Each of the narrower species and subgeneric groupings falling within the generic disclosure also form part of the disclosure. This includes the generic description of the embodiments with a proviso or negative limitation removing any subject matter from the genus, regardless of whether or not the excised material is specifically recited herein.

Unless the context requires otherwise or specifically stated to the contrary, integers, steps, or elements of the invention recited herein as singular integers, steps or elements clearly encompass both singular and plural forms of the recited integers, steps or elements.

The word “substantially” does not exclude “completely” e.g. a composition which is “substantially free” from Y may be completely free from Y. Where necessary, the word “substantially” may be omitted from the definition of the invention.

The invention illustratively described herein may suitably be practiced in the absence of any element or elements, limitation or limitations, not specifically disclosed herein. Thus, for example, the terms “comprising”, “including”, “containing”, etc. shall be read expansively and without limitation. Additionally, the terms and expressions employed herein have been used as terms of description and not of limitation, and there is no intention in the use of such terms and expressions of excluding any equivalents of the features shown and described or portions thereof, but it is recognized that various modifications are possible within the scope of the invention claimed. Thus, it should be understood that although the present invention has been specifically disclosed by preferred embodiments and optional features, modification and variation of the inventions embodied therein herein disclosed may be resorted to by those skilled in the art, and that such modifications and variations are considered to be within the scope of this invention.

The invention has been described broadly and generically herein. Each of the narrower species and subgeneric groupings falling within the generic disclosure also form part of the invention. This includes the generic description of the invention with a proviso or negative limitation removing any subject matter from the genus, regardless of whether or not the excised material is specifically recited herein.

Other embodiments are within the following claims and non-limiting examples. In addition, where features or aspects of the invention are described in terms of Markush groups, those skilled in the art will recognize that the invention is also thereby described in terms of any individual member or subgroup of members of the Markush group.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will be better understood with reference to the detailed description when considered in conjunction with the non-limiting examples and the accompanying drawings, in which

FIG. 1: Somatic Promoter Alterations in Primary Gastric Adenocarcinoma.

A) Example of an unaltered GC promoter. The UCSC genome track of the RHOA TSS (shaded box) highlights similar H3K4me3 signals in GC and matched normal samples. Similar signals are seen in GC lines. The bottom two tracks display similar levels of RNA expression in the same GC and matched normal sample (RNAseq). B) Example of a gained somatic promoter. The UCSC genome track of the CEACAM6 TSS (shaded box) highlights gain of H3K4me3 signals in GC samples and GC lines, compared to matched normal samples. In contrast, no changes are observed at the TSS of CEACAM5, an adjacent gene. Concordant tumor-specific gain of RNA expression is shown in the bottom 2 tracks displaying RNA-seq profiles of the same GC and matched normal samples. C) Example of a lost somatic promoter. The UCSC genome track of the ATP4A TSS (shaded box) highlights loss of H3K4me3 signals in GC samples and GC lines compared to matched normal samples. Concordant tumor-specific loss of RNA expression is shown in the bottom 2 tracks displaying RNA-seq profiles of the same GC and gastric normal samples. D) Heatmap of H3K4me3 read densities (row scaled) of somatic promoters (rows) in primary GCs and matched normal samples. E) Correlation between H3K4me3 promoter signals and H3K27ac activity signals in primary gastric samples (r=0.91, P<0.001). Each data point corresponds to a single H3K4me3 hi/H3K4me1 lo region. Analysis was performed using data from 16 N/T pairs (Table 4). F) Top 5 gene sets associated with canonical gained and lost somatic promoters. Genesets associated with genes up and downregulated in GC are rediscovered. Also note that gene sets related to H3K27me3 and SUZ12, a PRC2 component, are enriched.

FIG. 2: Association of Somatic Promoter Alterations with Gene Expression in GC and Other Tumor Types

A) Example of a GC somatic promoter. Example is for illustrative purposes only. B) Changes in RNA-seq expression (top) and DNA methylation (bottom) in discovery samples between somatic promoters and all promoters. Top—Boxplot depicting changes in RNA-seq expression between 9 paired primary GC and gastric normal samples at genomic regions exhibiting somatic promoters (gained and lost) (***P<0.001, Wilcoxon Test). Bottom—Boxplot depicting changes in DNA methylation (β-values) at regions exhibiting somatic promoters between 20 paired GC and gastric normal samples, compared to all promoters. (***P<0.001, Wilcoxon test) C) Independent Validation Cohorts. Boxplot depicting changes in RNA-seq expression at genomic regions exhibiting somatic promoters across 354 (321 GC, 33 normal) TCGA Stomach adenocarcinoma (STAD) samples, compared to all promoters (***P<0.001, Wilcoxon test) D) Somatic Promoters in Other Cancer Types. Boxplot depicting changes in RNA-seq expression at genomic regions exhibiting GC somatic promoters compared against all promoters, across 326 TCGA Colon adenocarcinoma (COAD) samples (286 COAD, 40 normal; ***P<0.001, Wilcoxon test), 170 TCGA kidney renal clear cell carcinoma (ccRCC) samples (98 ccRCC and 72 normal; ***P<0.001, Wilcoxon test), and 115 TCGA lung adenocarcinoma (LUAD) samples (58 LUAD, 57 normal; ***P<0.001 somatic gain vs all promoters and somatic gain vs. somatic loss, Wilcoxon test).

FIG. 3: Alternative Promoters in GC

A) UCSC browser track of the HNF4α gene. GC and matched gastric normal samples have equal H3K4me3 signals at the canonical HNF4α promoter. However, an alternative promoter, seen by H3K4me3 gain, can be observed at a downstream TSS in GCs compared to matched normals. At the RNA level, both in-house and TCGA STAD samples also show gain of gene expression at the alternate promoter TSS compared to normal samples. B) UCSC browser track of the EPCAM gene. Another example of alternative promoter usage at a downstream TSS. Gain of H3K4me3 is observed at a TSS downstream of the canonical promoter, while the canonical promoter exhibits equal H3K4me3 signals in GC and gastric normal. Gain of RNA-seq expression can also be observed in GC at the alternative promoter driven transcript in both in-house and TCGA STAD samples. C) UCSC browser track of the RASA3 gene, demonstrating H3K4me3 and RNA-seq signals highlighting gain of promoter activity at an un-annotated TSS (dark grey box) corresponding to a novel N-terminal truncated RASA3 transcript. Expression of this variant transcript was validated through 5′RACE in GC lines (bottom). D) Functional domains of the translated RASA3 canonical and alternate isoform. The alternate transcript is predicted to encode a RASA3 protein missing the RASGAP domain. E) Effect of overexpression of RASA3 canonical (CanT) and alternate (SomT) isoforms on the migration capability of SNU1967 (top) and GES1 (bottom) cells. Representative images of RASA3-Ctl (Empty vector), RASA3-CanT and RASA3-SomT in migration assays (n=3). Barplots show the % area of migrated cells vs the area of transwell membrane. Data is shown as mean±SD; n=3. (*P<0.05, **P<0.01, ***P<0.001, Student's one sided t-test)

FIG. 4: Somatic Promoter Alterations Exhibit Immunoediting Signatures

A) Schematic outlining alternative promoter usage leading to alternative transcript usage (Transcript box) and N terminally truncated protein isoforms (protein box). B) Barplot showing the average % of peptides with predicted high-affinity binding to MHC Class I (HLA-A, B, and C, IC<=50 nm). N-terminal peptides associated with recurrent somatic promoters (alternative promoters) show significantly enriched predicted MHC I binding compared to canonical GC peptides (P<0.01, Fisher's test), random peptides from the human proteome (P<0.001) and C-terminal peptides (P<0.01) derived from the same genes exhibiting the N-terminal alterations. Canonical peptides refer to peptides derived from protein coding genes overexpressed in GC through non-alternative promoters. C) Percentage (%) of high affinity peptides predicted to bind different HLA-alleles categorized by somatic gain or loss. Most alleles have a greater number of N-terminal lost peptides predicted to have high binding affinity. D) Quantification of somatic promoter expression using Nanostring profiling. Top—Distinct Nanostring probes were designed to measure expression of alternate and canonical promoter driven transcripts. 2 probes were designed for each gene—a canonical probe at the 5′ transcript marked by unaltered H3K4me3, and an alternate probe at the 5′ transcript of the somatic promoter. Bottom—Heatmap of alternative promoter expression from 95 GCs and matched normal samples. GC samples have been ordered left to right by their levels of somatic promoter usage. E) Association between Somatic Promoters and T-cell immune correlates (Singapore (SG) cohort). Top left—Expression of T-cell markers CD8A (P=0.1443) and the T-cell cytolytic markers GZMA (P=0.0001) and PRF1 (P=0.00806) in GC samples with either high or low somatic promoter usage (SG). Samples with high alternative promoter usage show lower expression of immune markers. All P values are from Wilcoxon one sided test. Right-Kaplan-Meier analysis comparing overall survival curves between validation samples with high somatic promoter usage (top 25%) and low somatic promoter usage (bottom 25%) (HR=2.56, P=0.02). F) Association of Somatic Promoters with T-cell Correlates in TCGA and ACRG Cohorts. (Left) Expression of T-cell markers CD8A (P=0.02), GZMA (P=0.01) and PRF1 (P=0.03) in TCGA STAD with either high or low somatic promoter usage. T-cell markers were evaluated by RNA-seq (Transcripts per million, Right) Expression of T-cell markers CD8A (P=0.035), GZMA (P=0.001) and PRF1 (P=0.025) in ACRG GC samples with either high or low somatic promoter usage. All P values are from Wilcoxon one sided test. G) EpiMAX Heatmap of total cytokine responses (Fold change relative to Actin) for 15 peptide pools against 9 donors. H) Individual cytokine responses against 15 peptides for two individual donors (Donor 2 and Donor 3) showing complex cytokine responses (FC2).

FIG. 5: Somatic Promoters are Associated with EZH2 Occupancy

A) Binding enrichment of ReMap-defined TFBSs at genomic regions exhibiting somatic promoters. TFs were sorted according to their binding frequency at all H3K4me3-defined promoter regions. EZH2 and SUZ12 binding sites significantly overlap regions exhibiting somatic promoters (gained and lost) (P<0.01, Empirical distribution test). B) Proportion of RNA transcripts associated with somatic promoters changing upon GSK126 treatment in IM95 cells, compared to RNA transcripts associated with unaltered promoters. The top somatic promoter figure is for illustrative purposes only. Unaltered promoters were defined as all gene promoters except the somatic promoters. The proportion of genes changing upon treatment, as a proportion of all genes, is also shown. Somatic promoters are more likely to change expression after GSK126 treatment relative to unaltered promoters (OR 1.46, P<0.001) or all GSK126 regulated genes (OR 9.21, P<0.001, Fisher Test) C) UCSC browser track of the SLC9A9 TSS, a gene with loss of promoter activity. Gain of expression is seen after inhibition of EZH2 using GSK126 in IM95 cells at both day 6 (D6) and Day 9 (D9) treatment. D) UCSC browser track of the PSCA TSS, with loss of promoter activity. Gain of expression is seen after inhibition of EZH2 using GSK126 in IM95 cells at both day 6 (D6) and Day 9 (D9) treatment.

FIG. 6: Somatic promoters reveal novel cancer-associated transcripts

A) Distribution of distances for different promoter categories to the nearest annotated TSSs. (left) The first barplot shows distance distributions for promoters present in gastric normal tissues, the second for promoter present in GC samples, and the third for promoters exhibiting somatic alterations (i.e. different in tumor vs normal). (right) The barplots present distance distributions associated with either lost or gained somatic promoters. A substantial proportion of gained somatic promoters occupy locations distant from previously annotated TSSs B) Median functional scores of unannotated promoters as predicted by GenoSkyline across 7 different tissues. Unannotated promoters exhibited high functional scores for GI, fetal and ESC tissues. C) Boxplot depicting average RNA-seq reads for CAGE-validated promoters, comparing either all promoters or somatic promoters and also supported by CAGE data. (**P<0.001, Wilcoxon one sided test). Somatic promoters are observed to have lower levels of RNA-seq expression. D) Cartoon depicting proposed effects of dynamic range on NanoChIP-seq and RNA-seq sensitivity in detecting lowly expressed transcripts. Due to a more restricted dynamic range, epigenomic profiling may detect active promoters missed by RNA-sequencing, due to the random sampling of abundantly expressed genes by RNAseq. E) Down and Up-sampling analysis. The y-axis depicts the number of transcripts detected that overlap either all promoters or somatic promoters at varying RNA-sequencing depths. Original primary sample RNA-seq data was sequenced at ˜106M reads which was down-sampled to 20M, 40M and 60M reads. Deep RNA-seq data was additionally generated at ˜139M read depth. F) Cancer-associated transcripts detected at deep but not regular RNA-seq depth. The UCSC genome browser track for ABCA13 shows an example of a novel transcript detected by NanoChIP-seq at a read depth of 20M but only detected by RNA-sequencing at read depth of ˜139M (Deep sequencing GC). This transcript is not detected by regular depth RNA-seq (GC).

FIG. 7: Chromatin Profiles of Primary GC

A) Chromatin profiles of primary GCs, matched normal gastric mucosae, and GC cell lines for 3 marks (H3K4me3, H3K27ac and H3K4me1). Shown are UCSC genome browser tracks of the GC driver gene MYC highlighting strong H3K4me3 and H3K27ac signals and low H3K4me1 at promoter locations B) H3K4me3, H3K27ac and H3K4me1 signal distributions at transcription start sites (TSS). Line plots show the distribution of chromatin signals for H3K4me3 hi/H3K4me1 lo regions at TSS regions (+/−3 kb). Heatmaps were plotted using ngs.plot(6) for the top 10,000 H3K4me3 hi/H3K4me1 lo regions C) Density distributions of H3K4me3:H3K4me1 ratios at identified H3K4me3 regions. All regions with H3K4me3/H3K4me1 ratios >1 were selected for further analysis (73%) D) Distribution of H3K4me3 hi/H3k4me1 lo regions against representative gene body features (top). The arrow represents the TSS. E) Enrichment of H3K4me3 hi/H3K4me1 lo regions against 15 chromatin states (columns) defined in different gastrointestinal tissues from the Epigenome Roadmap database (rows). Each column is scaled from 0 to 1. F) Overlap of H3K4me3 hi/H3K4me1 lo regions with FANTOMS CAGE data

FIG. 8: Epithelial features of GC promoters

A) Spearman correlation heat-map between H3K4me3 signals of primary GC, gastric normal samples (red type, highlighted by red arrow) and various tissue types from the Epigenome Roadmap database across all H3K4me3 hi/H3K4me1 lo regions B) Overlap of H3K4me3 hi/H3K4me1 lo regions with H3K4me3 regions identified in GC cell lines (87%), gastrointestinal fibroblast cells (61%) and colon carcinoma lines (74%)

FIG. 9: GC Somatic Promoter Features

A) Differential (somatic) H3K4me3 regions identified from 2 independent algorithms DESeq2 and edgeR. 96% of regions identified from DESeq2 overlapped those identified using edgeR. Both sets were pooled for subsequent analysis. B) Principal component analysis of 16 GC and gastric normal samples based on somatic promoters C) Heatmap of H3K27ac read densities across 16 GC and gastric normal samples across 1959 somatic promoters. D) Correlation between H3K4me3 promoter signals and H3K27ac activity signals in primary gastric samples for gained somatic (Left, r=0.78, p<0.001) and lost somatic (Right, r=0.82, p<0.001) promoters. Each data point corresponds to a single H3K4me3 hi/H3K4me1 lo region. Analysis was performed using data from 16 N/T pairs (Table 4). E) Volcano plot of somatic promoters (Top) highlighting the dynamic range of fold changes differences (x-axis) and the false discovery rate (FDR)-adjusted significance (−log 10 scale, y axis). The majority of the somatic promoters lie between FC 1 and 2.82, which likely reflects the dynamic range of Chip-seq. The Table (bottom) lists the number of somatic promoters identified at differing levels of stringency. Despite varying FDR thresholds, the majority of differential peaks are still preserved (e.g. 59% at q<0.01). F) Enrichment analysis of somatic promoters at varying fold change and FDR (q value) for top 5 genesets (FIG. 1F) associated with gained (red) and lost somatic promoters (blue). X axis reflects the −log 10 p value for gene-sets found to be enriched in subsets of somatic promoters. Even at stricter fold change (FC 2) and q-value thresholds (0.05, 0.01 and 0.001), similar GC specific and PRC2 associated signatures are still observed.

FIG. 10: Association of Somatic Promoters with Gene Expression in GC and Other Tumor Types

A) Example of a GC somatic promoter. Example is for illustrative purposes only. B) Changes in RNA-seq expression (top) and DNA methylation (bottom) discovery samples between somatic promoters and unaltered promoters. Top—Boxplot depicting changes in RNA-seq expression between 9 paired primary GC and gastric normal samples at genomic regions exhibiting somatic promoters (gained and lost) (***P<0.001, Wilcoxon Test). Bottom—Boxplot depicting changes in DNA methylation (β-values) at regions exhibiting somatic promoters between 20 paired GC and gastric normal samples, compared to unaltered promoters (***P<0.001, Wilcoxon test) C) Independent Validation Cohorts. Boxplot depicting changes in RNA-seq expression at genomic regions exhibiting somatic promoters across 354 (321 GC, 33 normal) TCGA Stomach adenocarcinoma (STAD) samples, compared to unaltered promoters (***P<0.001, Wilcoxon test) D) Somatic Promoters in Other Cancer Types. Boxplot depicting changes in RNA-seq expression at genomic regions exhibiting GC somatic promoters compared to unaltered promoters, across 328 TCGA Colon adenocarcinoma (COAD) samples (286 COAD, 40 normal; ***P<0.001, Wilcoxon test), 170 TCGA kidney renal clear cell carcinoma (ccRCC) samples (98 ccRCC and 72 normal; ***P<0.001, Wilcoxon test), and 115 TCGA lung adenocarcinoma (LUAD) samples (58 LUAD, 57 normal; ***P<0.001 Somatic gain vs unaltered and somatic gain vs somatic loss, *P<0.05 Somatic loss vs unaltered, Wilcoxon test).

FIG. 11: Changes in DNA methylation at CpG island containing promoters

A) Boxplot depicting changes in DNA methylation (β-values) at CpG island bearing somatic promoters between 20 paired GC and gastric normal samples, compared to all promoters bearing CpG islands (**P<0.001, Wilcoxon test)

FIG. 12: Expression distribution of alternative and canonical isoforms

A) Barplot showing distribution of T/N ratios of canonical and alternative transcript isoforms for all alternative transcripts (Global—top), HNF4α (middle), and EPCAM (bottom) using four independent quantification techniques, Cufflinks, MISO, Kallisto and NanoString. The Nanostring platform is introduced in FIG. 4 of the Main Text. ++ Nanostring analysis is confined to queried probes. (*P<0.05, **P<0.01, ***P<0.001, Wilcoxon one sided test). B) Boxplot showing the T/N ratio of N-terminal reads mapping to canonical promoters, compared to N-terminal reads mapping to alternative promoters. Alternative promoter driven transcripts exhibit significantly higher T/N ratios (p=0.04, Wilcoxon one sided test).

FIG. 13: Characterization of RASA3 Isoform

A) UCSC browser track of the RASA3 gene demonstrating H3K4me3 and RNA-seq signals at Somatic and Canonical TSSs. The Canonical TSS has equal signals while the Somatic TSS shows gain of promoter activity at an un-annotated TSS corresponding to a novel N-terminal truncated RASA3 transcript. B) UCSC browser track of the RASA3 gene demonstrating RNA-seq signals for the NCC24 GC cell line at Somatic and Canonical TSSs. NCC24 only expresses RASA3 SomT (also see C). C) Left—Identification of RASA3 SomT and CanT transcripts in NCC24 and NCC59 GC cells by 5′RACE. A third line (MKN1), was negative for RASA3 SomT as shown in the gel picture. A no-RNA template was run as a negative control. Right-Western Blot highlighting expression of RASA3 SomT protein in NCC24 cells. D) RAS GTP assays. (left) The Western blot shows levels of RAS in GES1 cells transfected with either empty vector (EV), RASA3 CanT or RASA3 SomT (n=3). GES1 cells were serum-starved overnight followed by serum stimulation for 30 minutes prior to harvest and a RAS-GTP pull down assay. Total RAS was measured in corresponding whole cell protein lysates. β-actin was used as a loading control. Positive (GTP) and negative (GDP) controls from the pull down assay are also shown. (right) The barplot quantifies active RAS intensity from three independent pull-down assays, performed in GES1 cells transfected with either empty vector (EV), RASA3 CanT or RASA3 SomT under FBS exposed conditions. Data is shown as mean±SD; n=3. (*P<0.05, Student's two sided t-test). E) Cell proliferation assays of SNU1967, GES1 and AGS cells after transfection with RASA3 CanT and SomT normalized to Day 0. (Data is shown as mean±SD performed in triplicate, representative of 3 independent experiments). F) Effect of overexpression of RASA3 CanT and SomT isoforms on the invasive capability of GES1 and SNU1967 cells. Representative images of EV, RASA3-WT and RASA3-Var in invasion assay (n=3). Barplot showing % area of invaded cells vs the area of transwell membrane. Data is shown as mean±SD; n=3. (*P<0.05, **P<0.01, ***P<0.001, Student's one sided t-test). G) Effect of overexpression of RASA3 CanT and SomT protein isoforms on the migration capability of highly migratory KRAS mutated AGS cells. Barplot showing % area of migrated cells vs the area of transwell membrane. Data is shown as mean±SD; n=3. (*P<0.05, **P<0.01, ***P<0.001, Student's one sided t-test). RASA3 WT induces more potent migration suppression than RASA3 Var, suggesting that RASA3 WT is a migration inhibitor. H) siRNA-mediated knockdown of RASA3 SomT in NCC24 cells. Cells were treated with sc-siRNA (control) and 2 RASA3 siRNAs (siRNA1-hs.Ri.RASA3.13 TriFECTa® Kit DsiRNA and siRNA-3-Silencer® Select Pre-Designed siRNA s355). (Left) Barplots showing fold change differences in mRNA expression of RASA3 SomT after treatment with siRNA-1 and siRNA-3. Data is shown as mean±SD; n=3. (Right) Western blotting results confirming RASA3 SomT protein reductions. Cells were harvested and lysed after 48 hrs of transfection. (***P<0.001, Student's one sided t-test). I) Effect of siRNA knockdown of RASA3 SomT isoform on the migration (left) and invasive (right) capability of NCC24 cells from two independent siRNAs. Representative images of sc-siRNA (control), siRNA-1, and siRNA-3 in migration and invasion assays (n=3). Barplot showing % area of migrated/invaded cells vs the area of transwell membrane. Data is shown as mean±SD; n=3. (*P<0.05, **P<0.01, ***P<0.001, Student's one sided t-test).

FIG. 14: Characterization of MET Isoforms

A) UCSC browser track of the MET gene, demonstrating H3K4me3 and RNA-seq signals highlighting gain of promoter activity at an alternative downstream locus (dark grey box). B) Functional domains of the MET canonical (WT) and alternative (Var) isoform. The alternative isoform is predicted to encode a MET protein with an N terminally truncated SEMA domain. C) Expression of MET (Var) transcripts in GC lines, as detected by 5′RACE. D) Western blot of HEK293 cells transfected with empty vector (EV), MET canonical full length (MET-WT) and truncated Variant (MET-Var) at 0, 15 and 30 minutes of HGF treatment (100 ng/ml) (n=3). GAB1, STAT3 and ERK1/2 are known downstream effectors of MET signaling. Number below each band is the quantified intensity using Image Lab. In both untreated and HGF-treated conditions, MET-Var transfected cells exhibited higher levels of p-Gab1 (Y627), a key mediator of MET signaling (2.48-3.95 fold, p=0.003 (untreated), p<0.05 (T15 and T30). In untreated samples, cells transfected with MET-Var also exhibited higher pERK1/2 levels (2.74 fold) and also higher p-STAT3 (Y705) levels (1.80 fold) compared to MET-WT (p=0.023 and p=0.026 for pERK and p-STAT3 (Y705) respectively). E) Bar graphs showing increase in pERK1/2 for EV, MET-WT and MET-Var at T0, T15 and T30, reflecting effects of HGF treatment. Data is shown as mean±SD; n=3. (*P<0.05, **P<0.01, ***P<0.001, Student's one sided t-test) F) Bar graphs showing increase in p-GAB1 (Y627), p-STAT3 (Y705), and pERK1/2 in cells transfected with MET-Var compared to EV and MET-WT. Graphs for all 3 time points are shown. Data is shown as mean±SD; n=3. (*P<0.05, **P<0.01, ***P<0.001, Student's one sided t-test)

FIG. 15: Immunogenicity of N-terminal peptides

A) Barplot showing average % of N-terminal peptides with predicted high-affinity binding to MHC Class I HLA-A (IC<=50 nm). As comparison, the figure in the Main Text represents average % s based on all three HLA classes (HLA-A, HLA-B, HLA-C). N-terminal peptides associated with recurrent somatic alternative promoters show significantly enriched predicted MHC I binding compared to canonical GC peptides (p<0.01), random peptides from human proteome and C-terminal peptides (p<0.001, Fisher's Test) derived from the same genes exhibiting the N-terminal alterations. B) MHC Binding Predictions using N-terminal peptides inferred by RNA-seq analysis alone. Annotated transcripts exhibiting different N-terminal exons in GC vs normals were identified using two different RNA-seq algorithms (DEXSeq(7) and Voom-diffsplice(8)) (FC>=2, FDR 0.05). This analysis identified 96 genes with potential alternative N-terminal transcripts, of which 46 (48%) were predicted to result in differing N terminal peptides (Purple bar).

FIG. 16: Immunogenicity Assay and Nanostring Profiling

A) Scatter plot of fold change (T vs N) of expression of alternate and canonical probes from NanoString and RNA-seq data of the same samples. An improved correlation is observed using the alternate probes B) Left—Expression of T-cell markers CD8A, GZMA and PRF1 in SG series (top), TCGA STAD (middle) and ACRG cohort (bottom) with high or low somatic promoter usage after adjustment of tumor purities as estimated by ASCAT. P values (Wilcoxon one sided test) are: CD8A—p=0.09 (SG), 0.004 (TCGA), 0.3 (ACRG); GZMA—0.0001 (SG), 0.002 (TCGA), 0.166 (ACRG), PRF1—0.013 (SG), 0.006 (TCGA), 0.3 (ACRG). Right—Expression of T-cell markers CD8A, GZMA and PRF1 in SG series (top), TCGA STAD (middle) and ACRG cohort (bottom) with high or low somatic promoter usage after adjustment of tumor content as estimated by ESTIMATE. p values (Wilcoxon one sided test) are: CD8A—p=0.28 (SG), 0.17 (TCGA), 0.37 (ACRG), GZMA—0.0005 (SG), 0.03 (TCGA), 0.09 (ACRG), PRF1—0.02 (SG), 0.22 (TCGA), 0.17 (ACRG). Samples with high alternative promoter usage are in red, while those with low usage are in blue. C) Kaplan-Meier analysis comparing overall survival curves between validation samples with high somatic promoter usage and low somatic promoter usage (split by median) (HR=1.81, P=0.04) D) Left—Expression of T-cell markers CD8A, GZMA and PRF1 in TCGA STAD with high or low somatic promoter usage after adjustment of mutation burden. P values (Wilcoxon one sided test) are: P=0.02 (CD8A), 0.01 (GZMA) and 0.03 (PRF1). Right—Expression of T-cell markers CD8A, GZMA and PRF1 in ACRG cohort with high or low somatic promoter usage after adjustment of mutation burden. P values (Wilcoxon one sided test) are: P=0.167 (CD8A), 0.009 (GZMA) and 0.03 (PRF1). E) Heatmap of alternative promoter expression from 264 ACRG GCs for all gained alternative promoters. GC samples have been ordered left to right by their levels of somatic promoter usage.

FIG. 17: Functional Assessment of Peptide Immunogenicity

A) Individual cytokine responses against 15 peptides for other normal donor PBMCs tested against different peptide pools. B) Experimental Immunogenicity Assay. Experimental design of in-vitro assay—i) Immature dendritic cells (DCs) cultured from CD14⁺ monocytes from HLA-A02:06 donors were differentiated in mature DCs (see Methods). Mature DCs were exposed to isogenic GC cell lysates (AGS cells) expressing Canonical (CanT) and Somatic (SomT) RASA3 isoforms. ii) Antigen presentation and T-cell activation: DCs presenting Can or Som RASA3 isoforms were co-cultured with HLA-matched T cells, resulting in T-cells primed against CanT or SomT RASA3. Primed T cells were then independently co-cultured with RASA3 CanT or RASA3 SomT expressing GC cells for two days, and markers of T-cell activation were assessed. C) Concentration of interferon-gamma (IFN-γ) secretion by co-culture of T cells primed with RASA3 CanT or SomT Isoforms, after antigen challenge. RASA3 CanT primed T cells released significantly more IFN-γ when co-cultured with RASA3 CanT expressing cells, compared to T cells primed with RASA3 SomT and co-cultured with RASA3 SomT expressing cells (P=0.02, representative of n=3 experiments). IFN-γ levels were determined by ELISA.

FIG. 18: EZH2 Inhibition

A) Barplot showing increased enrichment of EZH2 binding sites in HFE-145 cells at somatic promoters compared to all promoters (P<0.01). B) Growth curves of IM95 GC cells after GSK126 administration. Cell proliferation was monitored from 24 to 216 hours and represented relative to DMSO control treated cells (means±s.e.m. represents data from three experiments, and each experiment was performed in duplicate) C) Top 5 enriched curated gene sets (C2) for the set of genes identified from differential analysis of GSK126 treated vs DMSO control IM95 RNA-seq data at promoter loci. D) UCSC browser track of alternative promoter ESRRG with loss of promoter activity (GC (red) and normal gastric tissue (blue) H3K4me3). Gain of expression is seen after inhibition of EZH2 using GSK126 in IM95 cells at both day 6 (D6) and Day 9 (D9) treatment.

FIG. 19: Unannotated somatic promoters

A) Barplot showing fold enrichment of L1 (FC=8.02, P<0.001) and ERV1 (FC=2.78, P<0.001) repeat elements at unannotated promoter regions compared to all promoters B) Boxplot comparing H3K27ac signals (rpm) at unannotated somatic promoters with annotated somatic promoters. Unannotated somatic promoters have lower H3K27ac signals.

DETAILED DESCRIPTION OF THE PRESENT INVENTION

In a first aspect, the present invention refers to a method for determining the presence or absence of at least one promoter in a cancerous biological sample relative to a non-cancerous biological sample. The method comprises contacting the cancerous biological sample with at least one antibody or antibodies specific for histone modifications H3K4me3 and H3K4me1; isolating nucleic acid from the cancerous biological sample having a signal ratio of H3K4me3 relative to H3K4me1 greater than 1, wherein the isolated nucleic acid comprises at least one region or regions specific to said histone modifications; detecting a signal intensity of H3K4me3 in the isolated nucleic acid; and determining the presence or absence of at least one promoter in the cancerous biological sample based on the change in the signal intensity of H3K4me3 relative to the signal intensity of H3K4me3 in a non-cancerous biological sample.

In one embodiment, the cancerous and non-cancerous biological sample may comprise a single cell, multiple cells, fragments of cells, body fluid or tissue. In one embodiment the cancerous and non-cancerous biological sample may be obtained from the same subject.

In one embodiment, the cancerous and non-cancerous biological sample are each obtained from different subjects.

The contacting step in accordance with the method as described herein may comprise the immunoprecipitation of chromatin with the antibodies specific for the histone modifications. Examples of histone modification include but are not limited to H3K27ac, H3K4me3, H3K4me1. In a preferred embodiment, the histone modification is H3K4me3 and/or H3K4me1. In yet another embodiment, the histone modification is H3K27ac.

The method may further comprise mapping at least one promoter from the cancerous biological sample against at least one reference nucleic acid sequence to identify a gene transcript associated with the at least one promoter.

In some embodiments, the at least one reference nucleic acid sequence may comprise a nucleic acid sequence derived from: i) an annotated genome sequence; ii) a de novo transcriptome assembly; and/or iii) a non-cancerous nucleic acid sequence library or database.

In one embodiment, the change of signal intensity of H3K4me3 may be greater than a 0.5 fold, greater than a 1 fold, greater than a 1.5 fold, greater than a 2 fold, greater than a 2.5 fold or greater than a 3 fold increase or decrease relative to the signal intensity of H3K4me3 in the non-cancerous biological sample. In a preferred embodiment, the change of signal intensity of H3K4me3 may be greater than a 1.5 fold increase or decrease relative to the signal intensity of H3K4me3 in the non-cancerous biological sample. In another embodiment, the change of signal intensity of H3K4me3 greater than a 0.5 fold, greater than a 1 fold, greater than a 1.5 fold, greater than a 2 fold, greater than a 2.5 fold or greater than a 3 fold increase relative to the signal intensity of H3K4me3 in a non-cancerous biological sample, may correlate to the presence of at least one cancer-associated promoter in the cancerous biological sample.

In a preferred embodiment the change of signal intensity of H3K4me3 greater than a 1.5 fold increase relative to the signal intensity of H3K4me3 in a non-cancerous biological sample, may correlate to the presence of at least one cancer-associated promoter in the cancerous biological sample.

In one embodiment, the activity of the at least one cancer-associated promoter may correlate with an increase of SUZ12 or EZH2 binding sites relative to the total promoter population.

In one embodiment, an increase of SUZ12 or EZH2 binding sites correlates with an upregulation of activity of the at least one cancer-associated promoter. In another embodiment, the increase of SUZ12 or EZH2 binding sites correlates with a downregulation of activity of the at least one cancer-associated promoter.

In one embodiment, the at least one promoter may be a canonical promoter that is positioned within 100 bp, 200 bp, 300 bp, 400 bp, 500 bp, 600 bp, 700 bp, 800 bp, 900 bp or 1000 bp from a known gene transcript start site. In a preferred embodiment, the at least one promoter may be a canonical promoter that is positioned within 500 bp from a known gene transcript start site. The gene transcript start site may be associated with one or more of a cell-type specification gene, a cell adhesion gene, a cell mediated immunity gene, a gastric cancer-associated or deregulated gene, a PRC2 target gene or a transcription factor. In one embodiment, the gene transcript start site may be associated with an oncogene. The gene transcript start site may be associated with a gene selected from the group consisting of MYC, MET, CEACAM6, CLDN7, CLDN3, HOTAIR, PVT1, HNF4a, RASA3, GRIN2D, EpCAM and a combination thereof.

In one embodiment, the cancer is gastrointestinal cancer, gastric cancer or colon cancer.

In another embodiment, the at least one promoter may be an alternative promoter that may be associated with a canonical promoter, wherein the canonical promoter may be present in both the cancerous biological sample and the non-cancerous biological sample, and i) wherein the alternative promoter may be only present in the cancerous biological sample, or ii) wherein the alternative promoter may be only absent in the cancerous biological sample.

In some embodiments, the at least one promoter is an unannotated promoter that is positioned more than 100 bp, more than 200 bp, more than 300 bp, more than 400 bp, more than 500 bp away, more than 600 bp, more than 700 bp, more than 800 bp, more than 900 bp or more than 1000 bp from a gene transcript start site. In a preferred embodiment, the at least one promoter is an unannotated promoter that is positioned more than 500 bp away from a gene transcript start site.

In one embodiment, the method as described herein further comprises measuring the expression level of the at least one alternative promoter in the cancerous biological sample and non-cancerous biological sample, wherein the measuring comprises digital profiling of reporter probes; and determining the differential expression level of the at least one alternative promoter relative to the non-cancerous biological sample, based on the digital profiling of the reporter probes, to validate the presence or absence of at least one alternative promoter in the cancerous biological sample relative to a non-cancerous biological sample.

The step of measuring may be conducted using a NanoString™ platform.

In another aspect, the present invention provides a method for determining the prognosis of cancer in a subject. The method comprises contacting a cancerous biological sample obtained from the subject with at least one antibody or antibodies specific for histone modification H3K4me3 and H3K4me1; isolating nucleic acid from the cancerous biological sample having a signal ratio of H3K4me3 relative to H3K4me1 greater than 1, wherein the isolated nucleic acid comprises at least one region or regions specific to said histone modifications; detecting a signal intensity of H3K4me3 in the isolated nucleic acid; and determining the presence or absence of at least one cancer-associated promoter in the cancerous biological sample based on the change in the signal intensity of H3K4me3 relative to the signal intensity of H3K4me3 in a reference nucleic acid sequence, wherein the presence or absence of the at least one cancer-associated promoter in the cancerous biological sample is indicative of the prognosis of the cancer in the subject.

In one embodiment, the at least one cancer-associated promoter may be an alternative promoter that is associated with a canonical promoter, wherein the canonical promoter may be present in both the cancerous biological sample and the reference nucleic acid sequence, and i) wherein the alternative promoter may be only present in the cancerous biological sample, or ii) wherein the alternative promoter may be only absent in the cancerous biological sample.

The presence or absence of the at least one alternative promoter in the cancerous sample may indicative of a poor prognosis of cancer survival in the subject.

In one embodiment the method as described herein further comprises measuring the expression level of the at least one alternative promoter in the cancerous biological sample and the reference nucleic acid sequence, wherein the measuring comprises digital profiling of reporter probes; and determining the differential expression level of the at least one alternative promoter relative to the non-cancerous biological sample, based on the digital profiling of the reporter probes, to validate the presence or absence of at least one alternative promoter in the cancerous biological sample relative to the reference nucleic acid sequence.

The step of measuring may be conducted using a NanoString™ platform.

In another aspect the present invention provides a biomarker for detecting cancer in a subject, the biomarker comprising at least one promoter having a change in signal intensity of H3K4me3 in a cancerous biological sample relative to a non-cancerous biological sample.

In one embodiment, the at least one promoter comprises an increase of EZH2 binding sites relative to the total promoter population. In one embodiment, the at least one promoter may be hypomethylated. In another embodiment, the at least one promoter may be hypermethylated.

The at least one promoter may be a canonical promoter that is positioned less than 500 bp away from a gene transcript start site. In one embodiment, the gene transcript start site may be associated with one or more of a cell-type specification gene, a cell adhesion gene, a cell mediated immunity gene, a gastric cancer-associated or deregulated gene, a PRC2 target gene or a transcription factor. In one embodiment, the gene transcript start site may be associated with an oncogene.

In one embodiment, the gene transcript start site may be associated with a gene selected from the group consisting of MYC, MET, CEACAM6, CLDN7, CLDN3, HOTAIR, PVT1, HNF4α, RASA3, GRIN2D, EpCAM or a combination thereof.

In one embodiment, the at least one promoter may be an alternative promoter that may be associated with a canonical promoter, wherein the canonical promoter may be present in both a cancerous sample and a non-cancerous sample, and i) wherein the alternative promoter may be only present in a cancerous sample, or ii) wherein the alternative promoter may be only absent in a cancerous sample.

In one embodiment, the at least one promoter may be an unannotated promoter that may be positioned more than 100 bp, more than 200 bp, more than 300 bp, more than 400 bp, more than 500 bp, more than 600 bp, more than 700 bp, more than 800 bp, more than 900 bp or more than 1000 bp away from a gene transcript start site. In a preferred embodiment, the at least one promoter may be an unannotated promoter that may be positioned more than 500 bp away from a gene transcript start site.

In another aspect, there is provided a method for modulating the activity of at least one cancer-associated promoter in a cell, comprising administering an inhibitor of EZH2 to the cell. In another aspect there is provided a method for modulating the immune response of a subject to cancer, comprising administering to the subject an inhibitor of EZH2, wherein the EZH2 is associated with at least one cancer-associated promoter in the subject.

In one embodiment, the inhibitor of EZH2 may modulate the expression of immunogenic N-terminal peptides.

In one embodiment, the at least one cancer-associated promoter may be an alternative promoter that may be associated with a canonical promoter, wherein the canonical promoter may be present in both a cancerous sample and a non-cancerous sample, and i) wherein the alternative promoter may only be present in a cancerous sample, or ii) wherein the alternative promoter may only be absent in a cancerous sample.

In one embodiment, the alternative promoter is associated with a transcript variant, and wherein the transcript variant encodes a N-terminal protein variant.

In one embodiment, the N-terminal protein variant may be an N-terminal truncated protein or an N-terminal elongated protein. In one embodiment, the inhibitor of EZH2 may be a siRNA or a small molecule.

In one embodiment, the inhibitor of EZH2 may be GSK126.

In another aspect, there is provided use of an inhibitor of EZH2 in the manufacture of a medicament for modulating the activity of at least one cancer-associated promoter in a cell.

In another aspect there is provided use of an inhibitor of EZH2, wherein the EZH2 is associated with at least one cancer-associated promoter in the subject, in the manufacture of a medicament for modulating the immune response of a subject to cancer.

In another aspect, there is provided an inhibitor of EZH2 for use in modulating the activity of at least one cancer-associated promoter in a cell. In yet another aspect, there is provided an inhibitor of EZH2 for use in modulating the immune response of a subject to cancer, wherein the EZH2 is associated with at least one cancer-associated promoter in the subject.

In another aspect there is provided a method for determining the presence or absence of at least one cancer-associated promoter in a cancerous biological sample relative to a non-cancerous biological sample. The method comprises: contacting the cancerous biological sample with antibodies specific for histone modifications H3K4me3 and H3K4me1; isolating nucleic acid from the cancerous biological sample having a signal ratio of H3K4me3 relative to H3K4me1 greater than 1, wherein the isolated nucleic acid comprises regions specific to said histone modifications; detecting a signal intensity of H3K4me3 in the isolated nucleic acid at a read depth of 20M; and determining the presence or absence of at least one cancer-associated promoter in the cancerous biological sample based on the change in the signal intensity of H3K4me3 relative to the signal intensity of H3K4me3 in a non-cancerous biological sample.

EXPERIMENTAL SECTION

Methods and Materials

Primary Tissue Samples and Cell Lines

Primary patient samples were obtained from the SingHealth tissue repository with approvals from institutional research ethics review committees and signed patient informed consent. ‘Normal’ (non-malignant) samples used in this study refers to samples harvested from the stomach, from sites distant from the tumour and exhibiting no visible evidence of tumour or intestinal metaplasia/dysplasia upon surgical assessment. Tumor samples were confirmed by cryosectioning to contain >60% tumor cells. FU97, IM95, MKN7, OCUM1 and RERF-GC-1B cell lines were obtained from the Japan Health Science Research Resource Bank. AGS, KATOIII and SNU16, Hs 1.Int and Hs 738.St/Int gastrointestinal fibroblast lines were obtained from the American Type Culture Collection. NCC-59, NCC-24 and SNU-1967 and SNU-1750 were obtained from the Korean Cell Line Bank. YCC3, YCC7, YCC21, YCC22 were gifts from Yonsei Cancer Centre, South Korea. HFE145 cells were a gift from Dr. Hassan Ashktorab, Howard University. GES-1 cells were a gift from Dr. Alfred Cheng, Chinese University of Hong Kong. Cell line identifies were confirmed by STR DNA profiling using ANSI/ATCC ASN-0002-2011 guidelines. For our study, MKN7 cells, listed as a commonly misidentified cell line by ICLAC (http://iclac.org/databases/cross-contaminations/), exhibited a perfect match (100%) with MKN7 reference profiles in the Japanese Collection of Research Bioresources Cell Bank. All cell lines were negative for mycoplasma contamination as assessed by the MycoAlert™ Mycoplasma Detection Kit (Lonza) and the MycoSensor qPCR Assay Kit (Agilent Technologies). PBMCs from healthy donors were collected under protocol CIRB Ref No. 2010/720/E.

Nano-ChIPseq

Nano-ChIP-Seq was performed as described below.

Primary Tissue and Cell Line Fixation

Fresh-frozen cancer and normal tissues were dissected using a razor blade in liquid nitrogen to obtain—5 mg sized pieces for each ChIP. Tissue pieces were fixed in 1% formaldehyde/PBS buffer for 10 min at room temperature. Fixation was stopped by addition of glycine to a final concentration of 125 mM. Tissue pieces were washed 3 times with TBSE buffer. For cell lines, 1 million fresh harvested cells were fixed in 1% formaldehyde/medium buffer for 10 minutes (min) at room temperature. Fixation was stopped by addition of glycine to a final concentration of 125 mM. Fixed cells were washed 3 times with TBSE buffer, and centrifuged (5,000 r.p.m., 5 min).

ChIP

Pelleted cells and pulverized tissues were lysed in 100 μl 1% SDS lysis buffer and sonicated to 300-500 bp using a Bioruptor (Diagenode). ChIP was performed using the following antibodies: H3K4me3 (07-473, Millipore); H3K4me1 (ab8895, Abcam); H3K27ac (ab4729, Abcam).

WGA

After recovery of ChIP and input DNA, whole-genome-amplification was performed using the WGA4 kit (Sigma-Aldrich) and BpmI-WGA primers. Amplified DNAs were purified using PCR purification columns (QIAGEN) and digested with BpmI (New England Biolabs) to remove WGA adapters.

Library Preparation and Sequencing

30 ng of amplified DNA was used for each sequencing library preparation (New England Biolabs). 8 libraries were multiplexed (New England Biolabs) and sequenced on 2 lanes of a Hiseq2500 sequencer (Illumina) to an average depth of 20-30 million reads per library.

Sequencing reads were trimmed (10 bp from front and back) and mapped against human genome reference hg19 using the Burrows-Wheeler Aligner (BWA) (version 0.6.2) ‘aln’ algorithm. Reading statistics were generated using mapstat from samtools. We filtered reads based on their mapping quality (MAPQ>=10) and used uniquely mapped reads to perform peak calling using CCAT v3.0. We chose a MAPQ value of ≥10 because i) MAPQ≥10 has been previously reported as a reliable value for confident read mapping, ii) MAPQ≥10 has been recommended by the developers of the BWA-algorithm as a suitable threshold for confident mapping, and iii) independent studies comparing various read alignment algorithms have shown that mapping accuracies plateau at a 10-12 MAPQ threshold.

EZH2 ChIP-seq

Cells were cross-linked with 1% formaldehyde for 10 minutes at room temperature, and stopped by adding glycine to a final concentration of 0.2M. Chromatin was extracted and sonicated to ˜500 bp fragments. EZH2 antibodies (Catalog #5246, Cell Signaling) were used for chromatin immunoprecipitation (ChIP). 30 ng of ChIPed DNA was used for each sequencing library preparation (New England Biolabs). The library was sequenced on a Hiseq2500 (Illumina). Input DNA from cells prior to immunoprecipitation was used to normalize ChIP-seq peak calling. Prior to sequencing, qPCR was used to verify that positive and negative control ChIP regions were amplified in the linear range. Sequencing reads were mapped against human genome reference hg19 using the Burrows-Wheeler Aligner (BWA) (version 0.7) ‘aln’ algorithm. Reading statistics were generated using mapstat from samtools. We filtered reads based on their mapping quality (MAPQ>=10) and used uniquely mapped reads to perform peak calling using MACS2.

Quality Control Assessments of Nano-ChIPseq Data

ChIP Enrichment Assessment

We assessed ChIP library qualities (H3K27ac, H3K4me3 and H3K4me1) using two different methods. First, we estimated ChIP qualities, particularly H3K27ac and H3K4me3, by interrogating their enrichment levels at annotated promoters of protein-coding genes. Specifically, we computed median read densities of input and input-corrected ChIP signals around the transcription start sites (TSSs, +/−500 bp) of highly expressed protein-coding genes. For each sample, we then compared read density ratios of ChIP over input as a surrogate of data quality, retaining only those samples where the ChIP/input ratio was greater than 2-fold. Using this criteria, all H3K4me3 and H3K27ac samples (GC lines and primary samples) exhibited greater than 2-fold enrichment, indicating successful enrichment. Second, we used CHANCE (ChIp-seq ANalytics and Confidence Estimation), a software for ChIP-seq quality control and protocol optimization that indicates whether a ChIP library shows successful or weak enrichment. CHANCE assessment confirmed that the large majority (81%) of samples in our study exhibited successful enrichment. Quality status of each library, as assessed by both methods, are reported in Table 1.

TABLE 1 Read Mapping statistics of NanoChIP-seq libraries ChIP # of enrich- Peaks ment Total (FDR CHANCE around S. Patient Sample Library Histone Total Mapped <5%, Enrich- TSS No No Group ID ID Modification Reads Reads CCAT) ment (>2 Fold) 1 1 N 2000639 CHG023 H3K4Me1 116,179,997 56,009,114 11,438 successful yes 2 1 N 2000639 CHG079 H3K4Me3 144,760,092 45,662,594 13,301 successful yes 3 1 N 2000639 CHG022 H3K27Ac 107,005,238 47,688,264 30,155 successful yes 4 1 N 2000639 CHG021 Input 108,432,681 53,434,667 — — — 5 1 T 2000639 CHG019 H3K4Me1 139,751,844 62,529,719 9,133 successful yes 6 1 T 2000639 CHG078 H3K4Me3 176,761,815 52,219,714 15,417 successful yes 7 1 T 2000639 CHG018 H3K27Ac 125,811,014 56,636,793 22,220 successful yes 8 1 T 2000639 CHG017 Input 133,549,980 62,465,142 — — — 9 2 N 2000721 CHG081 H3K4Me3 123,984,264 41,723,243 13,046 successful yes 10 2 N 2000721 CHG031 H3K4Me1 142,898,092 61,716,210 17,896 successful yes 11 2 N 2000721 CHG030 H3K27Ac 142,881,448 56,328,103 24,624 successful yes 12 2 N 2000721 CHG029 Input 144,582,591 67,254,098 — — — 13 2 T 2000721 CHG080 H3K4Me3 128,094,707 52,416,345 12,751 successful yes 14 2 T 2000721 CHG026 H3K27Ac 132,143,844 52,416,345 45,274 successful yes 15 2 T 2000721 CHG027 H3K4Me1 120,824,194 54,688,706 48,701 successful yes 16 2 T 2000721 CHG025 Input 150,621,523 65,242,401 — — — 17 3 N 2000986 CHG083 H3K4Me3 145,813,278 44,476,466 13,305 successful yes 18 3 N 2000986 CHG039 H3K4Me1 112,190,461 52,061,916 14,977 successful yes 19 3 N 2000986 CHG038 H3K27Ac 136,195,033 47,671,991 26,993 successful yes 20 3 N 2000986 CHG037 Input 125,858,642 58,503,831 — — — 21 3 T 2000986 CHG082 H3K4Me3 199,735,230 48,070,517 13,296 successful yes 22 3 T 2000986 CHG035 H3K4Me1 99,757,592 48,602,649 25,882 successful yes 23 3 T 2000986 CHG034 H3K27Ac 127,564,120 45,231,776 29,278 successful yes 24 3 T 2000986 CHG033 Input 127,392,001 57,846,771 — — — 25 4 N 980437 CHG087 H3K4Me3 252,269,976 16,106,111 6,925 weak yes 26 4 N 980437 CHG089 H3K27Ac 248,399,140 21,095,856 20,018 weak yes 27 4 N 980437 CHG086 input 223,083,607 13,951,728 — — — 28 4 T 980437 CHG091 H3K4Me3 254,777,628 12,340,257 7,007 weak yes 29 4 T 980437 CHG093 H3K27Ac 215,915,787 19,054,278 48,614 weak yes 30 4 T 980437 CHG090 input 214,007,053 18,743,433 — — — 31 5 N 980097 CHG097 H3K27Ac 254,991,965 17,871,717 10,566 weak yes 32 5 N 980097 CHG094 Input 248,345,017 15,056,998 — — — 33 5 T 980097 CHG101 H3K27Ac 254,857,885 16,050,861 81,607 successful yes 34 5 T 980097 CHG098 Input 235,148,448 16,412,565 — — — 35 6 N 990068 CHG441 H3K4Me3 25,942,766 18,661,944 9,040 successful yes 36 6 N 990068 CHG443 H3K27Ac 28,993,775 20,404,671 30,306 successful yes 37 6 N 990068 CHG444 Input 16,583,307 14,164,125 — — — 38 6 T 990068 CHG437 H3K4Me3 19,295,687 15,981,638 23,546 successful yes 39 6 T 990068 CHG439 H3K27Ac 30,394,067 26,279,884 84,958 successful yes 40 6 T 990068 CHG440 Input 54,957,058 46,535,339 — — — 41 7 N 2000085 CHG449 H3K4Me3 22,207,074 17,120,624 13,421 weak yes 42 7 N 2000085 CHG451 H3K27Ac 31,752,518 26,505,029 93,432 successful yes 43 7 N 2000085 CHG452 Input 23,861,825 20,188,881 — — — 44 7 T 2000085 CHG445 H3K4Me3 27,386,842 17,898,292 16,274 successful yes 45 7 T 2000085 CHG447 H3K27Ac 37,833,126 29,893,873 67,464 successful yes 46 7 T 2000085 CHG448 Input 25,476,868 21,590,215 — — — 47 8 N 980401 GCC005 H3K4Me3 47,143,397 32,011,124 9,739 weak yes 48 8 N 980401 GCC006 H3K4Me1 49,813,057 38,517,830 29,304 successful yes 49 8 N 980401 GCC007 H3K27Ac 49,333,955 34,378,734 104,483 successful yes 50 8 N 980401 GCC008 Input 48,654,609 39,027,473 — — — 51 8 T 980401 GCC002 H3K4Me1 46,014,858 35,781,553 5,374 weak yes 52 8 T 980401 GCC001 H3K4Me3 40,037,248 16,724,980 11,773 successful yes 53 8 T 980401 GCC003 H3K27Ac 70,844,500 51,841,868 108,169 successful yes 54 8 T 980401 GCC004 Input 55,650,648 46,769,330 — — — 55 9 N 980447 GCC013 H3K4Me3 49,510,760 43,302,748 10,442 successful yes 56 9 N 980447 GCC014 H3K4Me1 51,911,778 46,524,450 18,916 weak yes 57 9 N 980447 GCC015 H3K27Ac 43,725,655 38,581,698 147,189 successful yes 58 9 N 980447 GCC016 Input 43,722,729 36,570,838 — — — 59 9 T 980447 GCC010 H3K4Me1 51,224,701 40,643,956 7,959 successful yes 60 9 T 980447 GCC009 H3K4Me3 41,895,137 28,002,598 9,325 weak yes 61 9 T 980447 GCC011 H3K27Ac 75,243,898 63,172,397 98,169 successful yes 62 9 T 980447 GCC012 Input 40,502,678 33,280,117 — — — 63 10 N 2001206 GCC021 H3K4Me3 42,094,067 35,485,202 12,682 successful yes 64 10 N 2001206 GCC022 H3K4Me1 44,213,793 38,760,554 50,615 weak yes 65 10 N 2001206 GCC023 H3K27Ac 47,356,714 34,355,781 112,565 successful yes 66 10 N 2001206 GCC024 Input 58,885,884 49,927,340 — — — 67 10 T 2001206 GCC017 H3K4Me3 48,193,228 36,729,294 13,835 successful yes 68 10 T 2001206 GCC018 H3K4Me1 43,730,845 35,480,758 44,504 weak yes 69 10 T 2001206 GCC019 H3K27Ac 52,518,766 42,398,517 111,758 successful yes 70 10 T 2001206 GCC020 Input 81,949,870 70,380,385 — — — 71 11 N 980436 GCC029 H3K4Me3 27,612,232 20,121,957 12,398 weak yes 72 11 N 980436 GCC030 H3K4Me1 22,983,565 20,452,059 53,077 weak yes 73 11 N 980436 GCC031 H3K27Ac 23,061,305 15,315,483 104,880 successful yes 74 11 N 980436 GCC032 Input 24,411,542 21,182,579 — — — 75 11 T 980436 GCC025 H3K4Me3 31,564,679 24,866,375 8,625 weak yes 76 11 T 980436 GCC026 H3K4Me1 51,645,661 38,028,800 58,456 successful yes 77 11 T 980436 GCC027 H3K27Ac 51,093,256 35,496,776 102,351 successful yes 78 11 T 980436 GCC028 Input 25,606,490 20,820,223 — — — 79 12 N 980417 GCC037 H3K4Me3 18,976,505 15,277,228 10,387 successful yes 80 12 N 980417 GCC039 H3K27Ac 30,443,642 25,447,390 70,910 successful yes 81 12 N 980417 GCC038 H3K4Me1 22,127,416 18,537,610 109,119 successful yes 82 12 N 980417 GCC040 Input 33,758,416 28,242,473 — — — 83 12 T 980417 GCC033 H3K4Me3 42,615,610 27,972,601 10,260 successful yes 84 12 T 980417 GCC035 H3K27Ac 33,438,272 29,141,996 76,369 successful yes 85 12 T 980417 GCC034 H3K4Me1 31,115,402 26,172,044 142,635 weak yes 86 12 T 980417 GCC036 Input 26,806,807 22,277,771 — — — 87 13 N 980319 GCC075 H3K4Me3 34,503,108 26,201,666 9,466 successful yes 88 13 N 980319 GCC076 H3K4Me1 32,308,832 28,194,660 56,964 weak yes 89 13 N 980319 GCC077 H3K27Ac 28,534,828 24,595,902 73,073 successful yes 90 13 N 980319 GCC078 Input 31,533,287 26,147,884 — — — 91 13 T 980319 GCC071 H3K4Me3 31,707,599 22,793,555 14,049 succesful yes 92 13 T 980319 GCC073 H3K27Ac 42,548,744 35,755,479 102,971 successful yes 93 13 T 980319 GCC072 H3K4Me1 28,112,304 24,361,418 196,347 weak yes 94 13 T 980319 GCC074 Input 28,895,896 24,529,014 — — — 95 14 N 990275 GCC088 H3K4Me3 39,968,810 31,536,231 7,964 successful yes 96 14 N 990275 GCC089 H3K27Ac 52,738,627 22,089,449 70,246 successful yes 97 14 N 990275 GCC090 Input 33,342,252 21,049,309 — — — 98 14 T 990275 GCC085 H3K4Me3 26,399,904 14,795,436 25,423 weak yes 99 14 T 990275 GCC086 H3K27Ac 45,712,891 25,668,453 183,458 successful yes 100 14 T 990275 GCC087 Input 40,285,061 32,790,063 — — — 101 15 N 2000877 GCC082 H3K4Me3 52,151,546 22,229,998 11,368 successful yes 102 15 N 2000877 GCC083 H3K27Ac 45,775,899 41,027,897 61,175 weak yes 103 15 N 2000877 GCC084 Input 38,226,148 30,117,584 — — — 104 15 T 2000877 GCC079 H3K4Me3 49,368,282 24,022,463 9,837 successful yes 105 15 T 2000877 GCC080 H3K27Ac 38,621,705 33,990,267 41,048 successful yes 106 15 T 2000877 GCC081 Input 38,824,621 32,814,299 — — — 107 16 N 20020720 GCC100 H3K4Me3 58,679,413 34,278,884 9,901 successful yes 108 16 N 20020720 GCC101 H3K27Ac 43,532,496 37,750,917 65,167 successful yes 109 16 N 20020720 GCC102 Input 39,544,734 31,454,551 — — — 110 16 T 20020720 GCC097 H3K4Me3 57,599,648 16,022,427 12,922 successful yes 111 16 T 20020720 GCC098 H3K27Ac 35,400,105 29,507,542 74,115 successful yes 112 16 T 20020720 GCC099 Input 37,092,424 29,452,932 — — — 113 17 N 20021007 GCC094 H3K4Me3 56,788,147 18,217,449 16,073 successful yes 114 17 N 20021007 GCC095 H3K27Ac 40,488,514 33,372,754 122,851 successful yes 115 17 N 20021007 GCC096 Input 40,712,616 34,440,613 — — — 116 17 T 20021007 GCC091 H3K4Me3 33,903,211 27,230,052 7,843 weak yes 117 17 T 20021007 GCC092 H3K27Ac 50,268,912 19,156,361 98,104 successful yes 118 17 T 20021007 GCC093 Input 34,936,961 29,417,989 — — — 119 CL1  FU97 FU97 GCC043 H3K27Ac 30,087,131 22,566,178 21,867 successful yes 120 CL1  FU97 FU97 GCC041 H3K4Me3 26,986,288 23,243,556 26,562 successful yes 121 CL1  FU97 FU97 GCC045 Input 33,566,067 23,430,741 — — — 122 CL10 RERF- RERF- CHG374 H3K27Ac 39,882,820 19,500,590 11,201 successful yes GC-1B GC-1B 123 CL10 RERF- RERF- CHG371 H3K4Me3 42,450,431 25,988,948 16,625 successful yes GC-1B GC-1B 124 CL10 RERF- RERF- CHG376 Input 21,437,700 16,948,709 — — — GC-1B GC-1B 125 CL11 SNU16 SNU16 CHG236 H3K27Ac 21,726,635 16,967,938 13,619 successful yes 126 CL11 SNU16 SNU16 CHG233 H3K4Me3 20,136,058 18,151,002 19,445 successful yes 127 CL11 SNU16 SNU16 CHG232 Input 19,522,181 14,558,761 — — — 128 CL12 SNU1750 SNU1750 CHG230 H3K27Ac 18,716,777 15,805,037 15,074 successful yes 129 CL12 SNU1750 SNU1750 CHG227 H3K4Me3 16,655,044 14,883,880 18,130 successful yes 130 CL12 SNU1750 SNU1750 CHG226 Input 19,602,424 13,575,272 — — — 131 CL13 YCC21 YCC21 CHG429 H3K27Ac 22,884,268 13,861,557 21,415 successful yes 132 CL13 YCC21 YCC21 CHG427 H3K4Me3 22,788,225 15,669,142 20,120 successful yes 133 CL13 YCC21 YCC21 CHG431 Input 40,378,916 34,747,778 — — — 134 CL13 YCC22 YCC22 GCC063 H3K27Ac 33,314,935 23,877,905 11,774 successful yes 135 CL13 YCC22 YCC22 GCC061 H3K4Me3 27,410,298 24,163,717 25,417 successful yes 136 CL13 YCC22 YCC22 GCC065 Input 26,685,596 18,976,555 — — — 137 CL14 YCC3  YCC3  GCC053 H3K27Ac 27,581,400 21,579,098 14,118 successful yes 138 CL14 YCC3  YCC3  GCC051 H3K4Me3 22,106,259 18,914,296 17,276 success yes 139 CL14 YCC3  YCC3  GCC055 Input 27,745,993 18,854,658 — — — 140 CL15 YCC7  YCC7  CHG424 H3K27Ac 38,599,550 22,445,268 32,770 successful yes 141 CL15 YCC7  YCC7  CHG422 H3K4Me3 19,594,480 14,546,474 22,521 successful yes 142 CL15 YCC7  YCC7  CHG426 Input 24,527,190 21,748,808 — — — 143 CL2  HFE145 HFE145 CHG245 H3K4Me3 24,122,708 19,760,850 18,492 successful yes 144 CL2  HFE145 HFE145 CHG244 Input 22,447,791 17,960,470 — — — 145 CL2  HFE145 HFE145 HFE145- H3K4Me3 50,701,700 45,821,209 17,299 weak — EZH2- MJ-5246 146 CL2  HFE145 HFE145 HFE145- Input 36,885,332 36,157,452 — — — input-MJ 147 CL3  Hs1.Int Hs1.Int HsInt- H3K4Me3 37,088,221 32,789,363 22,518 successful — K4me3. merged 148 CL3  Hs1.Int Hs1.Int HsInt-G- H3K4Me3 30,617,105 27,713,302 20,298 successful — (replicate) K4me3. merged 149 CL3  Hs1.Int Hs1.Int HsInt- Input 32,275,816 28,576,200 — — — input. merged 150 CL4  Hs738. Hs738. Hs738- H3K4Me3 37,945,394 33,334,651 150,552 successful — St/Int St/Int K4me3. merged 151 CL4  Hs738. Hs738.St/ Hs738- Input 32,275,816 24,581,922 — — — St/Int Int K4me3. merged 152 CL5  IM95 IM95 CHG434 H3K27Ac 23,309,435 9,168,213 27,692 successful yes 153 CL5  IM95 IM95 CHG432 H3K4Me3 25,179,506 14,069,213 19,956 successful yes 154 CL5  IM95 IM95 CHG436 Input 37,968,519 33,292,944 — — — 155 CL6  KATO3 KATO3 CHG242 H3K27Ac 24,559,532 17,356,721 28,730 successful yes 156 CL6  KATO3 KATO3 CHG238 Input 20,527,352 14,593,025 — — — 157 CL7  MKN7 MKN7 CHG419 H3K27Ac 35,301,333 30,804,178 24,268 successful yes 158 CL7  MKN7 MKN7 CHG417 H3K4Me3 28,119,400 24,793,006 23,766 successful yes 159 CL7  MKN7 MKN7 CHG421 Input 35,839,896 31,791,610 — — — 160 CL8  NCC59 NCC59 CHG218 H3K27Ac 22,973,156 19,828,610 14,937 successful yes 161 CL8  NCC59 NCC59 CHG215 H3K4Me3 15,642,441 13,907,147 12,410 successful yes 162 CL8  NCC59 NCC59 CHG214 Input 17,926,188 13,139,789 — — — 163 CL9  OCUM1 OCUM1 CHG212 H3K27Ac 24,573,737 20,570,185 17,284 successful yes 164 CL9  OCUM1 OCUM1 CHG209 H3K4Me3 19,557,872 17,178,274 15,445 successful yes 165 CL9  OCUM1 OCUM1 CHG208 Input 20,585,679 16,680,529 — — —

Promoter Analysis

Promoter (H3K4Me3 hi/H3K4Me1 lo) regions were identified by calculating the H3K4Me3:H3K4Me1 ratio for all H3K4Me3 regions merged across normal and GC samples. We estimated the required sample size to achieve 80% power and 10% type I error (http://powerandsamplesize.com/) based on the average signals of top 100 differential promoters between tumor and normal samples. This result yielded a recommended sample size of 11 (average), which is met in our study (16 N/T). Regions with H3K4Me3:H3K4Me1 ratios <1 in both normal and GC samples were excluded from further analysis. For all analyses performed in this study, promoter regions were defined as genomic locations exhibiting H3K4me3 hi/me1 low signals, and for all subsequent analyses, it was only within this pre-defined H3K4me3 hi/me1 low subset that H3K4me3 signals were compared. H3K27ac data was used for correlative analysis. H3K4me3 data (fastqs) for colon carcinoma lines was downloaded from public databases—Hct116 and Caco2 from ENCODE and V503 and V400 from GSE36204. To compare promoter signals between GC and normal samples, we used the DESeq2 and edgeR bioconductor packages using a read count matrix of chipseq signals, adjusting for replicate information. Regions with fold changes greater than 1.5 (FDR 0.1) were selected as significantly different. The criteria of FC 1.5 and q<0.1 was based on previous literature comparing ChIP-seq profiles using DESeq2 and edgeR also using similar thresholds. Significantly altered promoters identified by DESeq2 overlapped almost completely with altered promoters found by edgeR. A regularized log transformation of the DESeq2 read counts was used to plot PCAs and heatmaps.

Transcriptome Analysis

RNA-seq data was obtained from the European Genome-phenome Archive under Accession No: EGAS00001001128. Data was processed by first aligning to GENCODE v19 transcript annotations using TopHat v2.0.12. Cufflinks 2.2.0 was used to generate FPKM abundance measures. For identification of novel transcripts, Cufflinks was used without employing a reference transcript annotation. Transcripts were then merged across all GC and normal samples and compared against GENCODE annotations to identify novel transcripts using Cuffmerge 2.2.0. Deep-depth strand-specific RNA sequencing was also performed on 10 additional primary samples. Total RNA was extracted using the Qiagen RNeasy Mini kit, and RNA-seq libraries were constructed according to manufacturer's instructions using Illumina Stranded Total RNA Sample Prep Kit v2 (Illumina, San Diego, Calif., USA) Ribo-Zero Gold option (Epicentre, Madison, Wis., USA), and 1 ug total RNA. Sequencing was performed using the paired-end 101 bp read option. TCGA datasets were downloaded from TCGA Data Portal (https://tcga-data.nci.nih.gov/tcga) in form of fastq files which were then aligned to GENCODE v19 transcript annotations using TopHat v2.0.12. To analyze promoter-associated RNA expression, RNA-seq reads from TCGA samples (tumors and normals) were mapped against the genomic locations of promoter regions originally defined by epigenomic profiling in the discovery samples, including all promoters, gained somatic promoters, and lost somatic promoters (see FIG. 1 in Main Text). RNA-seq reads mapping to these epigenome-defined promoter regions were then quantified, normalized by promoter length (kilobases) and by total library size, and fold changes in expression were computed between tumor and normal TCGA sample groups. Length of promoter loci was defined as the number of base pairs (bps) between the start and stop genomic coordinate of the H3K4me3 region as identified by the peak caller program CCAT v3.0. (190) Isoform level quantification for alternative promoter driven transcripts was performed using cufflinks (FPKM), Kallisto (TPM) and MISO (isoform centric analysis). Assigned counts for each isoform were normalized by DESeq2.

DNA Methylation Analysis

Genomic DNA of gastric tumors and matched normal gastric tissues was extracted (QIAGEN) and processed for DNA methylation profiling using Illumina HumanMethylation450 BeadChips (HM450). Methylation β-values were calculated and background corrected using the methylumi R BioConductor package. Normalization was performed using the BMIQ method (wateRmelon package in R). CpG island locations were downloaded from the UCSC genome browser. Overlaps of at least 1 bp between promoter loci and CpG islands were identified using BEDTools intersect. For each group (all promoters, gained somatic promoters and lost somatic promoters), we identified probes overlapping the predicted promoter regions and calculated average beta value differences. A two-sample Wilcoxon test was performed.

Survival Analysis

Kaplan-Meier survival analysis was used with overall survival as the outcome metric. Log-rank tests were used to assess the significance of the Kaplan-Meier analysis.

Gene Set Enrichment Analysis

Gene set enrichment analysis was performed using MsigDB by computing the overlap of genes associated with somatic promoters against the C2 set of curated genes.

Mass Spectrometry and Data Analysis

Peptide level mass spectrometry data for 90 colon and rectal cancer (CRC) samples and 60 normal colon epithelium samples were downloaded from the CPTAC portal generated by the Clinical Proteomic Tumor Analysis Consortium (NCl/NIH). (https://cptac-data-portal.georgetown.edu/cptac). Spectral counts were extracted using IDPicker's idQuery tool. Differentially expressed peptides were identified by fitting a linear model (limma R) on quantile normalized and log₂ transformed spectral counts. For GC cell line mass spectrometry, AGS, GES-1, SNU1750 and MKN1 cells were extracted with RIPA buffer supplemented with protease inhibitor. 150 μg protein extract of each biological quadruplicate (i.e. 4 replicates per cell line) were separated on a 12% NuPAGE Novel Bis-Tris precast gel (Thermo Scientific). For in-gel digestion, samples were separated into two fractions and reduced in 10 mM DTT for 1 h at 56° C. followed by alkylation with 55 mM iodoacetamide (Sigma) for 45 min in the dark. Tryptic digests were performed in 50 mM ammonium bicarbonate buffer with 2 μg trypsin (Promega) at 37° C. overnight. Peptides were desalted on StageTips and analysed by nanoflow liquid chromatography on an EASY-nLC 1200 system coupled to a Q Exactive HF mass spectrometer (Thermo Fisher Scientific). Peptides were separated on a C18-reversed phase column (25 cm long, 75 μm inner diameter) packed in-house with ReproSil-Pur C18-QAQ 1.9 μm resin (Dr Maisch). The column was mounted on an Easy Flex Nano Source and temperature controlled by a column oven (Sonation) at 40° C. A 225-min gradient from 2 to 40% acetonitrile in 0.5% formic acid at a flow of 225 nl/min was used. Spray voltage was set to 2.4 kV. The Q Exactive HF was operated with a TOP20 MS/MS spectra acquisition method per MS full scan. MS scans were conducted with 60,000 and MS/MS scans with 15,000 resolution. For data analysis, raw files were processed with MaxQuant version 1.5.2.8 against the UNIPROT annotated human protein database. Carbamidomethylation was set as a fixed modification while methionine oxidation and protein N-acetylation were considered as variable modifications. Search results were processed with MaxQuant filtered with a false discovery rate of 0.01. The match between run option and LFQ quantitation were activated. LFQ intensities were filtered for potential contaminants, reverse proteins and log_(e) transformed. They were then imputed using open source software Perseus (0.5 width, 1.8 downshift) and fitted using linear models (limma R).

5′ RACE and Gene Cloning

5′ Rapid amplification of cDNA ends (5′ RACE) was performed using the 5′ RACE System for Rapid Amplification of cDNA Ends, Version 2 (Invitrogen, 18374-058). Briefly, 2 μg of total RNA was used for each reverse transcription reaction with SuperScript™ II reverse transcriptase and gene-specific primer 1 for each gene. After cDNA synthesis, RNase mix (RNase H and RNase T1) was used to degrade the RNA. First strand cDNAs were then purified with S.N.A.P. columns, and tailed with dCTP and TdT. dC-tailed cDNAs were amplified using the abridged anchor primer and nested gene-specific primer 2 by Go Taq®Hot Start Polymerase (Promega, M5001). Subsequently, primary PCR products were reamplified with the abridged universal amplification primer (AUAP), and gene-specific primer 3. Gel electrophoresis was performed. PCR bands of interest were excised and purified for cloning with the TA Cloning Kit (Invitrogen, K2020). A minimum of 12 independent colonies were isolated, and purified plasmid DNA was sequenced bi-directionally on an ABI 3730 DNA analyzer (Applied Biosystems) (Table 2). Constructs for MET transcripts were generated by PCR amplification of full-length cDNAs encoding wild type and variant MET from KATOIII cells. Wild type and variant RASA3 full-length transcripts were PCR amplified from NCC59 cells. cDNA fragments were cloned into the pCI-Puro-HA vector (modified from Promega's pCI-Neo vector, a gift from Wanjin Hong, Institute of Molecular and Cell Biology, Singapore). Plasmids were transiently transfected into cell lines using Lipofectamine 3000 (Thermo Scientific).

TABLE 2 RACE Primers Gene Gene Gene specific specific specific Gene primer 1 primer 2 primer 3 RASA3 5′GGAGTAGATACGC 5′CACAGCCAGTG 5′CTTCTCCACTG TCCGT3′ GCCGCTCAGGTA3′ CCAGGATGTT3′ (SEQ ID  (SEQ ID  (SEQ ID NO: 1837) NO: 1838) NO: 1839) MET 5′TAGGAGAATGTAC 5′GGAGACACTGG 5′CGAGAAACCAC TGTAT 3′ ATGGGAGTC 3′ AACCTGCAT3′ (SEQ ID  (SEQ ID  (SEQ ID NO: 1840) NO: 1841) NO: 1842)

Western Blotting

3×10⁵ HEK293 cells were seeded and transfected using Lipofectamine 3000 (Thermo Scientific). Cells were serum starved for 16 hours before addition of human HGF (R&D systems, 100 ng/ml) for 0, 15 and 30 minutes, and immediately harvested with cold Triton-X100 Lysis Buffer (50 mM Tris pH 8.0, 150 mM NaCl, 1% Triton X-100) with protease and phosphatase inhibitors (Roche) on ice. Protein concentration was measured by Pierce BCA protein assay (Thermo Scientific). Cell lysates were heated at 95° C. for 10 min in SDS sample buffer and 20 μg of each cell lysate was loaded per well. Proteins were transferred to nitrocellulose membranes. Western blotting was performed by incubating membranes 4 hrs at room temperature with the following antibodies: Met & β-actin (Santa Cruz), p-MET (Y1234/1235 & Y1349), pSTAT3 (S727 & Y705), STAT3, ERK, p-ERK, Gab1, pGab1 (Y627) (Cell Signaling). Membranes were incubated in secondary antibodies at 1:3,000 for 1 hr at room temperature and developed with SuperSignal West Femto Maximum Sensitivity substrate (Thermo Scientific) using ChemiDoc™ MP Imaging System (BIO-RAD). Western blot bands were quantified using Image Lab software (BIO-RAD). Experiments were repeated in triplicate.

Cell Proliferation Assays

3×10³ GES1, SNU1967 and AGS cells were plated into 96-well plates in media with 10% fetal bovine serum and left overnight to attach. The next day (Day 0), cells were transiently transfected with wild-type and variant RASA3 constructs using Lipofectamine 3000 (Thermo Scientific). The amount of the constructs was 40 ng/well for AGS and 100 ng/well for GES1 and SNU1967 cells. Cell proliferation was measured by the WST-8 assay (Cell Counting Kit-8, Dojindo) from 24 to 120 hours post-transfection. 10 uL of WST-8 solution was added per well and the absorbance reading was measured at 450 nm after 2 hours of incubation in a humidified incubator.

Transfection with RASA3 siRNAs

Two RASA3 siRNAs were used to silence the RASA3 SomT transcript in NCC24 cells (hs.Ri.RASA3.13.1 TriFECTa® Kit DsiRNA Duplex (Integrated DNA Technologies), and Silencer® Select Pre-Designed siRNA s355 (Life Technologies)). NCC24 cells were transfected either with the above two siRNAs or a non-targeting control (ON-TARGETplus Non-targeting pool, Dharmacon) at a final concentration of 100 nM for 48 hours, subsequently followed by qPCR and western validation and migration/invasion assays.

Migration and Invasion Assays

To determine cell migratory capacities, RASA3 wild type and variant transfected AGS and GES1, SNU1967 and AGS, and siRNA treated NCC24 cells were tested using Corning Costar 6.5 mm Transwell with 8.0 μm Pore Polycarbonate Membrane Inserts (3422, Corning, N.Y., USA). 2.5×10⁴ AGS cells and 2×10⁴ GES1 cells, 3×10⁴ SNU1967 cells and 5×10⁴ NCC24 cells were suspended in 0.1 ml serum-free RPMI medium and added to the top of the Transwell insert. 0.6 ml RPMI containing 10% FBS was added into the bottom well as a chemoattractant. After incubation for 24 h at 37° C. in a 5% CO2 incubator, cells were fixed with 3.7% formaldehyde and permeabilized with 100% methanol. Non-migrated cells were scraped off with cotton swabs from the upper surface of the membrane. Migrated cells were stained with 0.5% crystal violet. The number of migrated cells were represented as the total area of migrated cells vs the area of transwell membrane calculated using ImageJ software. For cell invasion assays, the above Transwell inserts were coated with 0.1 ml (300 μg/mL) Corning Matrigel matrix (354234, Corning, N.Y., USA) for 2 to 4 h at 37° C. before use. All subsequent steps were identical to the migration assay protocol.

Measurement of RASA3 mRNA Levels

Total RNA was extracted from three independent experiments using the Qiagen RNAeasy mini kit according to manufacturer's instructions. RNA was reverse transcribed using Improm-II™ Reverse Transcriptase (Promega). Real time PCR was performed in triplicate using Quantifast SYBR Green PCR kit (Qiagen) on an Applied Biosystems HT7900 Real Time PCR System. Fold change was calculated using the Delta Ct method and normalised to β-actin. Primer sequences are as follows. β-actin: F-5′ TCCCTGGAGAAGAGCTACG 3′ (SEQ ID NO: 1843), R-5′ GTAGTTTCGTGGATGCCACA 3′ (SEQ ID NO: 1844); RASA3 SomT: F-5′ TTGTGAGTGGTTCAGCGGTA 3′ (SEQ ID NO: 1845), R-5′ TCAAGCGAAACCATCTCTTCT 3′ (SEQ ID NO: 1846).

RAS-GTP Assay

GES1 cells were transfected with either RASA3 CanT, RASA3 SomT or empty vector for 48 hours. Cells were harvested for protein in FBS containing media or subjected to over-night serum starvation followed by serum stimulation for 30 minutes prior to harvest. Proteins were extracted using ice-cold lysis buffer (Active RAS Pull-down and Detection Kit) containing protease inhibitor cocktail (Nacalai Tesque). Active RAS fraction was obtained using the Active RAS Pull-down and Detection Kit (Thermo Fisher Scientific) according to manufacturer's instructions. Total RAS was measured in corresponding whole cell protein lysates. B-actin was used as a loading control. Protein concentrations were determined using the Pierce BCA protein assay (Thermo Scientific). SDS sample buffer was added to the lysates and boiled at 100° C. for 5 minutes. Samples were loaded in each well of a 4-15% Mini-Protean TGX gel (Biorad) and transferred to a PVDF membrane using a semi-dry blotting system (Biorad). Membranes were probed with anti-RAS (1 in 200 dilution, supplied in Active RAS Pull-down and Detection Kit), or B-actin (1 in 5000 dilution, Sigma A5316) in 5% milk-PBST at 4° C. over-night. Secondary anti-mouse antibody (LNA931, Amersham) was used at a dilution of 1 in 2000 for 1 hour at room temperature. Membranes were developed using Amersham ECL Prime Western Blotting Detection Reagent and imaged using a Chemidoc Imaging system (Biorad).

Altered Peptide and Antigen Prediction

Altered peptides were defined as variant N-terminal protein sequences arising from somatic alterations in alternative promoter usage. The following filters were applied to select the pool of altered peptides—i) Fold change of at least 1.5 for alternate vs. canonical RNA-seq expression ii) Only one canonical and one alternate isoform per gene loci iii) Annotated transcripts are confirmed as protein coding by Gencode. Canonical promoters were defined as regions exhibiting unaltered H3K4me3 peaks. Random peptides from the human proteome were generated from amino acid sequences of Gencode coding transcripts. N-terminal peptide gains were identified as cases where the alternative transcript was associated with a different 5′ region predicted to result in a different translated protein sequence compared to the canonical transcript. For each N terminal altered protein, we evaluated binding of 9-mer peptides using the NetMHCpan 2.8 using a strict threshold of IC<=50 nm to identify strong MHC binders. N-terminal gained peptides were mapped against protein assembly data of the same gene to evaluate protein expression. Antigen predictions were performed against HLA types of 13 GC samples predicted using OptiType. OptiType was run using default parameters except BWA mem was used as an aligner for pre-filtering reads aligning to the Optitype provided reference sequences. 3 samples with poor coverage and unpaired reads with mismatches were omitted from analysis. Eleven HLA-A, HLA-B, and HLA-C allelic variants of increased prevalence in the South East Asian population (HLA-A*02:07/HLA-A*11:01/HLA-A*24:02/HLA-A*33:03/HLA-A*24:07, HLA-B*13:01/HLA-B*40:01/HLA-B*46:01, HLA-C*03:04/HLA-C*07:02/HLA-C*08:01) were obtained from the Allele Frequency Net Database (http://www.allelefrequencies.net).

Association of Cytolytic Markers with Alternative Promoter Usage

Local immune cytolytic activity was evaluated using the expression of Granzyme A (GZMA) and Perforin (PRF1). Tumor content was estimated using two algorithms—ASCAT(79) (aberrant cell fraction) and ESTIMATE (tumor purity). Expression data for the SG series was downloaded (GSE15460) and normalized using the robust multi-array average algorithm in the ‘affy’ R package and log_(e) transformed. Affymetrix SNP Array 6.0 data for the SG series was downloaded from GSE31168 and GSE85466. Mutation frequencies for TCGA STAD samples were downloaded from the TCGA STAD publication data (https://tcga-data.nci.nih.gov/docs/publications/stad_20140 using level 2 curated MAF files (QCv5_blacklist_Pass.aggregated.capture.tcga.uuid.curated.somatic.maf) filtered for “Missense” variant classification. Expression data for TCGA STAD samples (TPM) was computed using the kallisto algorithm. Raw SNP Array 6.0.CEL files for TCGA gastric cancers (STAD) were downloaded from the GDC data portal (https://gdc-portal.nci.nih.gov/). Access to this dataset was obtained using dbGaP credentials and an ID issued by eRA commons. Precomputed ESTIMATE scores for TCGA STAD were downloaded from http://bioinformatics.mdanderson.org/estimate/and converted to tumor purity using the formula cos (0.6049872018+0.0001467884×ESTIMATE score). Preprocessed expression data for the ACRG series was downloaded from GSE62254, and pre-computed ASCAT scores obtained from collaborators (JL). Expression of cytolytic markers was adjusted for missense mutation and tumor purity frequencies using a spline regression model.

Peptides and Cells for Cytokine Assays

A set of peptides for 15 representative alternative promoters was purchased from GenScript (GenScript). Peptide sequences and composition of peptide pools for each alternative promoter are described in Table 3. Control peptide pools for human Actin were purchased from JPT (PM-ACTS, PepMix™ Human (Actin) JPT). Peripheral blood mononuclear cells (PBMCs) were obtained from 9 healthy volunteers of whom 8 PBMC samples were HLA-typed (Table 3).

TABLE 3 HLA types of healthy PBMC donors Sample HLA-A HLA-B HLA-C Donor 1 A*11:01 A*24:02 B*15:01 B*51:01 C*04:01 C*14:02 Donor 2 A*11:01 A*33:03 B*40:01 B*58:01 C*03:02 C*07:02 Donor 3 A*03:01 A*33:03 B*35:03 B*38:01 C*12:03 C*12:03 Donor 4 A*02:07 A*24:07 B*15:02 B*46:01 C*01:02 C*08:01 Donor 5 A*02:03 A*11:01 B*15:02 B*51:01 C*08:01 C*14:02 Donor 6 A*02:01 A*68:01 B*15:13 B*40:06 C*08:01 C*15:02 Donor 7 A*02:07 A*33:03 B*27:04 B*58:01 C*03:02 C*12:02 Donor 8 A*02:03 A*11:01 B*38:02 B*46:01 C*01:02 C*07:02 Donor 9 Not determined

EpiMAX Assay

PBMCs were labelled with 1 μM CFSE (Life Technologies, Thermo Fisher Scientific) and cultured at a density of 200,000 cells per well in complete culture medium (cRPMI comprising RPMI 1640 medium (Gibco, Thermo Fisher Scientific), 15 mM HEPES (Gibco), 1% non-essential amino acid (Gibco), 1 mM sodium pyruvate (Gibco), 1% penicillin/streptomycin (Gibco), 2 mM L-glutamine (Gibco), 50 μM β2-mercaptoethanol (Sigma, Merck), and 10% heat-inactivated FCS (Hyclone)) for 5 days. Individual peptide pools of each alternative promoter were added at the start of the culture at a concentration of 1 μg/ml for each peptide. At the end of day 5, cells were stained with LIVE/DEAD® fixable near-IR dead cell stain kit (Life Technologies), and labelled with CD4-BUV737 (BD), CD8-PacificBlue (BD), CD3-PE (BioLegend), CD19-PE/TexasRed (Beckman), and CD56-APC (BD). Analysis of T cell proliferation by CFSE dilution was performed by flow cytometry using a LSRII (BD). In addition, magnetic bead-based cytokine multiplex analysis (human cytokine panel 1, Millipore, Merck) was performed on cell culture supernatants to measure secreted cytokine levels.

IFN-γ Assay

To test the immunogenicity of the RASA3 WT and Variant protein sequences, CD14⁺ monocytes were isolated from a HLA-A*02:06 donor by positive selection using magnetic beads (Miltenyi, Germany). Dendritic cells were generated by GM-CSF (1000 IU/ml) and IL-4 (400 IU/ml), and further matured by TNF (10 ng/ml), IL-1b (10 ng/ml), IL-6 (10 ng/ml) (Miltenyi, Germany) and PGE2 (1 μg/ml) (Stemcell Technologies, Canada) for 24 hours. The DCs were then primed with AGS cell lysates expressing WT RASA3 or Variant RASA3 for 24 hours, before being co-cultured with T cells from the same donor at the ratio of 1:5. After 5 days of co-culture with DC, T cells were isolated by positive selection using CD3 magnetic beads (Miltenyi, Germany) and co-cultured with AGS cells expressing either WT or Variant RASA3 at the ratio of 20:1 for two days. Supernatants were harvested and IFN-γ release was measured by ELISA (R&D, USA).

NanoString Analysis

Nanostring nCounter Reporter CodeSets were designed for 95 genes (83 upregulated in GC and 11 downregulated) and 5 housekeeping genes (AGPAT1, CLTC, B2M, POL2RL and TBP covering a broad expression range) on the SG series samples. For each gene, we designed 3 probes, targeting a) the 5′ end of the alternate promoter location, b) the 5′ end of the canonical promoter (defined by promoter regions of equal enrichment in both GC and normal samples OR the longest protein coding transcript) and c) a common downstream probe. Vendor-provided nCounter software (nSolver) was used for data analysis. Raw counts were normalized using the geometric mean of the internal positive control probes included in each CodeSet.

A separate NanoString assay was designed for 88 genes on the ACRG cohort. For each gene, we designed 3 probes, targeting a) the 5′ end of the alternate promoter location, b) the 5′ end of the canonical promoter (defined by promoter regions of equal enrichment in both GC and normal samples OR the longest protein coding transcript).

Repeat Enrichment Analysis

Repetitive element families over-represented at regions exhibiting somatic promoter alterations were identified using RepeatMasker annotations from the UCSC Table Browser (GRCh37/hg19). “Unknown”, “Simple_Repeat” and “Satellite” annotations were filtered from the repeat set. Repetitive elements were included only if they overlapped a promoter by a minimum of 50%. Enrichment of repetitive element families was assessed using a binomial test with Benjamini-Hochberg FDR correction and all promoter regions were used as the background.

Functional Prediction Analysis

Genome wide and tissue specific functional scores were downloaded from GenoCanyon (http://genocanyon.med.yale.edu/GenoCanyon_Downloads.html, Version 1.0.3) and GenoSkyline (http://genocanyon.med.yale.edu/GenoSkyline) respectively. Overlaps were calculated using bedtools IntersectBed and functional scores over each unannotated somatic promoter were computed.

Transcription Factor Enrichment

Transcription factor binding sites for 237 TFs were obtained from the ReMap database, a public database of ENCODE and other public Chip-seq TFBS data sets. Overlaps were calculated and counted against the somatic promoter set. Relative enrichment scores were calculated as ratio of (#bases in state and overlap feature)/(#bases in genome) and [(#bases overlap feature)/(#bases in genome)×(#bases in state)/(#bases in genome)].

EZH2 Inhibition

IM95 were treated with GSK126 (Selleck, USA), a selective EZH2 inhibitor, at a concentration of 5 uM. Cell proliferation was monitored in 96-well plates post-treatment with GSK126 using the CellTiter-Glo® Luminescent Cell Viability Assay (Promega) for three independent experiments. For RNA-seq analysis, total RNA was extracted using the Qiagen RNAeasy mini kit according to manufacturer's instructions. Cells were treated with GSK126 (Selleck, USA; dissolved in DMSO) at a concentration of 5 uM. Control cells were treated with the same concentration of DMSO (0.1%). RNAseq differential analysis for promoter loci was carried out using edgeR on read counts mapping to H3K4me3 regions estimated using featureCounts. RNAseq gene level differential analysis was performed using cuffdiff2.2.1.

Additional Information

Accession codes: Genomic data for this study has been deposited in the National

Center for Biotechnology GEO database, under accession numbers GSE51776 and GSE75898. (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=kfoxqeamzftpal&acc=GSE75898)

Results

Identifying Epigenomic Promoter Alterations in GC

Using NanoChIP-seq, we profiled three histone modification marks (H3K4me3, H3K27ac and H3K4me1) across 17 GCs, matched normal gastric mucosae (34 samples) and 13 GC cell lines, generating 110 epigenomic profiles (Tables 1 and 4 provide clinical and sequencing metrics) (FIG. 1a ). Quality control of the Nano-ChIPseq data was performed using two independent methods: ChIP-enrichment at known promoters, and employing the ChIP-seq quality control and validation tool CHANCE (CHip-seq ANalytics and Confidence Estimation). Comparisons of Nano-ChIPseq read densities at 1,000 promoters associated with highly expressed protein-coding genes confirmed successful enrichment in all H3K27ac and H3K4me3 libraries. CHANCE analysis also revealed that the large majority (81%) of samples exhibited successful enrichment (Table 1). We have previously also shown that Nano-ChIP signals exhibit a good concordance with orthogonal ChIP-qPCR results.

TABLE 4 Clinicopathological Parameters of samples used Site Sample of Stage Stage Stage Stage Lauren's EBV TCGA ID Platform Age Gender Tumor (T) (N) (M) AJCC7 Grade Classification status Subtype 20021007 ChIPseq + 53.8 male GE T2b N0 m0 2A poorly intestinal type unknown GS Infinium450K junction differentiated adenocarcinoma 20020720 ChIPseq + 75.2 male antrum T2a N1 m0 2A moderately intestinal type unknown CIN Infinium450K differentiated adenocarcinoma 2001206 ChIPseq + 64.8 male antrum T4a N3b m1 4 poorly diffuse type unknown C!N Infinium450K differentiated adenocarcinoma 2000877 ChIPseq + 44.6 male cardia T2a N1 m0 2A poorly intestinal type unknown CIN Infinium450K differentiated adenocarcinoma 2000085 ChIPseq + 52.6 male lesser T2 N0 m0 1B moderately intestinal type yes GS Infinium450K curve differentiated adenocarcinoma 990275 ChIPseq + 71.6 male lesser T4a N0 m0 2B moderately intestinal type no CIN Infinium450K curve differentiated adenocarcinoma 990068 ChIPseq + 73.3 male body T4a N2 m0 3B poorly intestinal type no GS Infinium450K differentiated adenocarcinoma 980447 ChIPseq + 68.8 male lesser T4a T3b m1 4 poorly intestinal type unknown CIN Infinium450K curve differentiated adenocarcinoma 980436 ChIPseq + 65.0 female lesser T4a N1 m0 3A moderately intestinal type unknown GS Infinium450K curve differentiated adenocarcinoma 980401 ChIPseq + 82.9 female unknown T4a N1 m0 3A poorly diffuse type unknown GS Infinium450K differentiated adenocarcinoma 980319 ChIPseq + 67.8 male unknown T4a N1 m0 3A poorly mixed/ yes GS Infinium450K differentiated OTHERS 2000986 ChIPseq + 39.0 female pylorus T4a T3b m1 4 poorly diffuse type unknown GS Infinium450K + differentiated adenocarcinoma RNA-seq 2000721 ChIPseq + 70.9 male lesser T4a T3b m1 4 poorly diffuse type yes GS Infinium450K + curve differentiated adenocarcinoma RNA-seq 2000639 ChIPseq + 69.5 male lesser T4a N3a m1 4 moderately intestinal type yes GS Infinium450K + curve differentiated adenocarcinoma RNA-seq 980437 ChIPseq + 67.8 female incisura T4a T3b m0 3C poorly intestinal type unknown CIN Infinium450K + differentiated adenocarcinoma RNA-seq 980417 ChIPseq + 67.0 male lesser T4a T3b m0 3C poorly diffuse type yes GS Infinium450K + curve differentiated adenocarcinoma RNA-seq 980097 ChIPseq + 65.4 male unknown T2 N1 m0 2A undifferentiated mixed/ unknown EBV Infinium450K + OTHERS RNA-seq 980418 Infinium450K 88.0 male greater T4a N2 m0 3B moderately intestinal type unknown — curve differentiated adenocarcinoma 57689477 RNA-seq 84.5 female greater T1b N0 m0 1A moderately intestinal type no — curve differentiated adenocarcinoma 43658255 RNA-seq 66.6 male antrum T4a N3a m1 4 moderately intestinal type unknown — differentiated adenocarcinoma 2000892 RNA-seq 71.3 female lesser T2 N1 m0 2A moderately intestinal type no — curve differentiated adenocarcinoma

To enable accurate promoter identification, we integrated data from multiple histone modifications, selecting H3K4me3 regions simultaneously co-depleted for H3K4me1⁴² (“H3K4me3 hi/H3K4me1 lo regions”; FIG. 7, Methods). Comparisons against data from external sources, including GENCODE reference transcripts, ENCODE chromatin-state models, and CAGE (CAP analysis gene expression) databases, validated the vast majority of H3K4me3 hi/H3K4me1 lo regions as true promoter elements (see section titled “Validation of H3K4me3 hi/H3K4me1 lo regions as true promoters” and FIG. 7). Because primary gastric tissues comprise several different tissue types, including epithelial cells, immune cells, and stroma, we further confirmed that our promoter profiles were reflective of bona fide gastric epithelia by comparisons against Epigenome Roadmap data for gastric and non-gastric tissues. Gastric tumor and matched normal promoter profiles exhibited the highest correlations to Roadmap gastric mucosae, and were distinct from other gastrointestinal tissues (small intestine, colon mucosa, colon sigmoid), stomach-associated muscle, skin, and blood (CD14) (FIG. 8). Primary tissue promoter profiles also showed a significant overlap with promoter profiles of GC cell lines (87%), which are purely epithelial in origin, compared to gastrointestinal fibroblast lines (58-69%), and colon carcinoma lines (59-74%) (FIG. 8).

In total, we mapped ˜23,000 promoter elements in the Nano-ChIPseq cohort. Visual exploration of these promoter elements identified three main promoter categories—unaltered promoters, promoters gained in tumors (gained somatic or tumor-specific promoters), and promoters present in normal gastric tissues but lost or decreased in GC (lost somatic or normal-specific promoters) (FIG. 1a-c ). Representative examples of unaltered promoters included RhoA (FIG. 1a ), while CEACAM6, an intracellular adhesion gene, exhibited somatic promoter gain at the CEACAM6 transcription start site (TSS) in tumor samples and cell lines (FIG. 1b ). Conversely, ATP4A, a parietal cell-associated H+/K+ ATPase with decreased expression in GC⁴³, exhibited somatic promoter loss (FIG. 1c ). Both CEACAM6 and ATP4A promoter alterations were correlated with increased and decreased CEACAM6 and ATP4A gene expression in the same samples respectively (FIGS. 1b and 1c ).

Previous studies have established distinct molecular subtypes of GC. Due to limited sample sizes however, we elected in the current stay to identify promoter alterations (“somatic promoters”) present in multiple GC tissues relative to control tissues irrespective of subtype. Focusing on recurrent alterations also has the benefit of reducing potential artefacts due to “private” epigenomic variation or individual sample-specific technical errors. Using two complementary read-count based algorithms commonly used for analysis of ChIP-seq data, we identified ˜2000 highly recurrent somatic promoters, of which 75% were gained in GCs (FC 1.5, q<0.1). Two-dimensional heat-map clustering and principal components analysis (PCA) plots based on somatic promoters confirmed a separation of GCs from normal samples based on promoter alterations (FIG. 1d and FIG. 9). Somatic promoter H3K4me3 levels were also highly correlated with H3K27ac signals (r=0.91, P<0.001, FIG. 1e ), commonly regarded as a marker of active regulatory activity. This correlation was observed across all somatic promoters (r=0.84, P<0.001, FIG. 1E), and also when gained somatic and lost somatic promoters were analyzed separately (r=0.78, P<0.001 for gained somatic; r=0.82, P<0.001 for lost somatic, FIG. 9). Pathway analysis revealed that both gained somatic and lost somatic promoters were significantly associated with expression genesets previously reported to be up and downregulated in GC respectively (FIG. 10. These included upregulated oncogenes (MET, ABL2), cell adhesion genes (CEACAM6) and claudin family members (CLDN7, CLDN3). 15-18% of somatic promoters mapped to non-coding RNAs (ncRNAs), including HOTAIR and PVT1, previously associated with GC (Table 5). Additional analyses at increasing thresholds of stringency (FC from 1.5-2 and FDR from 0.1-0.001) yielded similar results, supporting the robustness of this analysis (FIG. 9). These results demonstrate that normal gastric epithelia and GCs can be distinguished on the basis of epigenomic promoter profiles.

TABLE 5 Non coding RNAs associated with Altered promoters Gene H3K4Me3 (T/N) AC004158.2 Gain AC004870.4 Gain AC005281.1 Gain AC005550.4 Gain AC007040.5 Gain AC007392.3 Gain AC009229.6 Gain AC012531.23 Gain AC016683.6 Gain AC016995.3 Gain AC019201.1 Loss AC068134.6 Gain AC069277.2 Gain AC073479.1 Loss AC079779.4 Loss AC090051.1 Loss AC092296.1 Gain AC092594.1 Gain AC092635.1 Loss AC096579.1 Loss AC096579.13 Loss AC096579.7 Loss AC116351.2 Gain AC128653.1 Loss AC131951.1 Loss AC133680.1 Loss AC140912.1 Gain AC144521.1 Gain AF127936.5 Loss AJ003147.8 Gain AL031721.1 Gain AL109618.1 Gain AL122015.1 Gain AL122127.1 Loss AL122127.2 Loss AL122127.3 Loss AL122127.4 Loss AL122127.5 Loss AL139319.1 Gain AP000525.9 Gain AP001065.15 Gain C11orf95 Gain C1orf132 Loss CASC9 Gain CCAT1 Gain CECR7 Loss CT49 Gain CTB-175P5.4 Gain CTC-228N24.1 Gain CTC-276P9.1 Loss CTC-480C2.1 Gain CTD-2008P7.9 Loss CTD-2147F2.1 Gain CTD-2201E18.5 Gain CTD-2314B22.1 Gain CTD-2314B22.3 Gain CTD-2532K18.1 Gain CTD-2591A6.2 Gain FENDRR Loss FZD10-AS1 Gain GS1-179L18.1 Gain GS1-259H13.2 Gain H19 Gain hsa-mir-4537 Loss hsa-mir-4538 Loss hsa-mir-4539 Loss JRK Loss LINC00237 Gain LINC00278 Loss LINC00355 Gain LINC00365 Loss LINC00393 Gain LINC00665 Gain LINC00668 Gain LINC00669 Gain LINC00675 Loss LINC00858 Gain LINC00898 Gain LINC00939 Gain LINC00960 Gain MIR1184-1 Gain MIR135B Gain MIR144 Loss MIR196B Gain MIR3147 Gain MIR3185 Gain MIR31HG Loss MIR4488 Gain MIR4634 Gain MIR663A Gain MIR663B Loss MIR935 Gain MLLT4-AS1 Gain PVT1 Gain RN7SKP258 Gain RN7SL773P Gain RNA5S17 Gain RNA5SP18 Gain RNA5SP19 Gain RNA5SP75 Loss RNU1-92P Gain RNVU1-10 Gain RP11-108K3.1 Gain RP11-138J23.1 Gain RP11-13A1.1 Gain RP11-161I10.1 Gain RP11-163N6.2 Gain RP11-168L22.2 Gain RP11-16E12.2 Loss RP11-177F15.1 Gain RP11-191L9.4 Gain RP11-211C9.1 Gain RP11-229C3.2 Loss RP11-246A10.1 Gain RP11-25H12.1 Gain RP11-276H19.2 Gain RP11-288G11.3 Loss RP11-299P2.1 Loss RP11-2E17.1 Loss RP11-308B16.2 Gain RP11-326A19.4 Gain RP11-346D19.1 Gain RP11-347D21.4 Gain RP11-348J24.2 Gain RP11-351J23.2 Gain RP11-356J5.12 Gain RP11-357H14.17 Gain RP11-371I1.2 Gain RP11-137D17.1 Gain RP11-395B7.2 Gain RP11-3J1.1 Gain RP11-400N13.2 Gain RP11-403I13.5 Gain RP11-408B11.2 Gain RP11-426L16.8 Gain RP11-431M3.1 Loss RP11-434D9.2 Gain RP11-43F13.4 Gain RP11-44H4.1 Gain RP11-44N12.5 Gain RP11-451B8.1 Gain RP11- Gain 453F18_B.1 RP11-460N16.1 Gain RP11-469L4.1 Loss RP11-472N13.2 Gain RP11-48O20.4 Loss RP11-499F3.2 Gain RP11-514D23.1 Loss RP11-547I7.2 Gain RP11-575F12.1 Gain RP11-576D8.4 Gain RP11-599B13.3 Loss RP11-608O21.1 Gain RP11-60A8.1 Gain RP11-61G19.1 Gain RP11-626G11.4 Gain RP11-626H12.1 Gain RP11-627G23.1 Loss RP11-632K5.3 Gain RP11-66B24.2 Gain RP11-66B24.7 Gain RP11-689K5.3 Gain RP1-170O19.14 Gain RP1-170O19.17 Gain RP11-776H12.1 Gain RP11-79P5.7 Gain RP11-809C18.5 Gain RP11-81H14.2 Loss RP11-831A10.2 Loss RP11-834C11.14 Gain RP11-834C11.6 Loss RP11-867G2.6 Gain RP11-89F3.2 Gain RP11-933H2.4 Gain RP11-963H4.3 Loss RP1-274L7.1 Gain RP13-137A17.4 Loss RP13-137A17.6 Loss RP13-379O24.3 Loss RP1-63G5.5 Gain RP1-79C4.4 Gain RP3-522D1.1 Gain RP4-562J12.2 Gain RP4-594A5.1 Gain RP5-1077H22.2 Loss RP5-1121A15.3 Gain RP5-884M6.1 Gain RP5-916L7.2 Gain RP6-114E22.1 Gain SNORA31 Gain SNORA48 Gain SNORD56B Loss snoU13 Gain SOX21-AS1 Loss TPTEP1 Loss TTTY15 Loss U3 Loss U8 Loss

Validation of H3K4Me3 Hi/H3K4Me1 Lo Regions as True Promoters

Four lines of evidence support the vast majority of H3K4me3 hi/H3K4me1 lo regions as true promoters. First, H3K4me3 hi/H3K4me1 lo regions were strongly enriched at genomic locations located 1 kb upstream of known GENCODE transcription start sites (TSSs) (FIG. 7). Second, at TSS regions, H3K4me3 signals exhibited a classical skewed bimodal intensity pattern, previously reported to be associated with promoters (FIG. 7). Third, when overlapped with regions defined by the Epigenomic Roadmap (EpiRd) 15 state model, we observed significant enrichments of H3K4me3 hi/H3K4me1 lo regions at proximal promoter states (TSSs/Regions flanking transcription sites) in gastrointestinal tissues relative to other tissues (FIG. 7). Fourth, CAGE (CAP analysis gene expression) is a specialized transcriptome sequencing method used to map gene promoters using 5′ mRNA data. Integration with CAGE data from the FANTOMS consortium revealed an 81% overlap of H3K4me3 hi/H3K4me1 lo regions with robust CAGE tag clusters. (FIG. 7).

Somatic Promoters in GC Exhibit Deregulation in Diverse Cancer Types

To explore relationships between epigenomic promoter alterations and gene expression, we analyzed RNA-seq data from the same discovery cohort (˜106 million reads/sample), quantifying RNA-seq transcript reads mapping to the epigenome-guided promoter regions or directly downstream. Examining somatic promoter regions (FIG. 2A provides an illustrative example of a gained somatic promoter), we observed significantly increased expression at gained somatic promoters in GCs, and significantly decreased expression at lost somatic promoters, compared to either all promoters (P<0.001, FIG. 2B), or unaltered promoters (P<0.001, FIG. 10). Among other types of epigenetic modifications, previous studies have also reported a reciprocal relationship between active regulatory regions and DNA methylation. Using Infinium 450K DNA methylation arrays, we identified 7,505 CpG sites overlapping somatic promoter regions (5,213 sites for gained somatic promoters, 2,292 sites for lost somatic promoters). Promoters gained in GC were significantly hypomethylated compared to all promoters, (P<0.001, Wilcoxon test) while promoters lost in GC were hypermethylated (P<0.001, Wilcoxon test) (FIG. 2b , bottom). As DNA methylation typically occurs in CpG rich regions, (56) we then repeated the analysis focusing only on CpG island bearing promoters (Methods and Materials). Similar to the original results, CpG island bearing promoters gained in GC were significantly hypomethylated compared to all CpG island bearing promoters, (P<0.001, Wilcoxon test) while CpG island bearing promoters lost in GC were hypermethylated (P<0.001, Wilcoxon test) (FIG. 11).

To validate the somatic promoter alterations in a larger independent GC cohort and also to examine their behavior in other cancer types, we proceeded to query RNA-seq data of 354 GC samples from the TCGA consortium (n=321 GC, n=33 matched normals). To perform this analysis, RNA-seq reads from TCGA samples were mapped against the epigenome-guided somatic promoter regions defined by the discovery samples, and normalized to calculate fold change differences in expression in GC vs. normals (see Methods and Materials). Similar to the discovery series, we observed that TCGA GCs also exhibited significantly increased expression at gained somatic promoters, while lost somatic promoters exhibited decreased expression, relative to either all promoters (P<0.001, FIG. 2C) or unaltered promoters (P<0.001, FIG. 10). We further tested the tissue-specificity of the GC somatic promoters by querying RNA-seq data from other tumor types, including colon, kidney renal clear cell carcinoma (ccRCC), and lung adenocarcinoma (LUAD) (FIG. 2d ). Almost two-thirds (n=1231, 63%, FC=1.5) of GC somatic promoters were also differentially regulated in TCGA colon cancer samples and similarly, a significant proportion of GC somatic promoters were also associated with differential RNA-seq expression in TCGA ccRCC (n=939, 48%, FC=1.5) and LUAD samples (n=1059, 54%, FC=1.5) (FIG. 2D). This result suggests that many GC somatic promoters are also likely associated with deregulated promoter activity in other solid epithelial malignancies.

Role of Alternative Promoters

By comparing the somatic promoters against the reference Gencode database (V19), we discovered extensive use of alternative promoters (18%) in GCs, defined as situations where a common unaltered promoter is present in both normal tissues and tumors (canonical promoter) but a secondary tumor-specific promoter is engaged in the latter (alternative promoter). The remaining 82% of somatic promoters corresponded to single major isoforms or unannotated transcripts (see later). 57% of the alternative promoters occurred downstream of the canonical promoter. Using multiple RNA-seq analysis methods, we confirmed that transcript isoforms driven by alternative promoters are overexpressed in GCs to a significantly greater degree than canonical promoters in the same gene (Methods and Materials, FIG. 12). For example, HNF4α, a transcription factor overexpressed in GC, is driven by two promoters (P1 and P2). At the HNF4α canonical promoter (“P2”), we observed equal promoter signals in GCs and normal tissues; however we also further observed gain of an additional promoter in GCs at a transcription start site 45 kb downstream (“P1”). Similar HNF4α P1 promoter gains were also observed in GC cell lines (FIG. 3a ), with RNA-seq analysis supporting HNF4α P1 isoform expression in GCs. Alternative promoter usage was also observed at the EpCAM gene, frequently used to identify circulating tumor cells, causing expression of EpCAM transcript ENST00000263735.4 (FIG. 3b ). Notably, both the HNF4α and EpCAM alternative isoforms exhibited significantly greater cancer overexpression compared to their canonical isoforms (FIG. 12). Other genes associated with tumor-specific alternative promoters, many reported for the first time, including NKX6-3 (FC 1.83, q<0.05) and GRIN2D (FC 1.9, q<0.001). A complete list of GC tumor-specific promoters is provided (Table 6).

TABLE 6 Alternative Promoters Change H3K4Me3 in Loci (T/N) Type protein Gene chr2: 69900550-69901900 Loss Alternate 1 AAK1 chr2: 44058400-44060450 Gain Alternate 1 ABCG5 chr1: 179108750- Gain Alternate 1 ABL2 179113100 chr1: 6451200-6453300 Gain Alternate 1 ACOT7 chr7: 991700-995250 Gain Alternate 1 ADAP1 chr11: 69811750- Gain Alternate 1 ANO1 69814800 chr19: 50308050- Gain Alternate 1 AP2A1 50309350 chr17: 36620950- Gain Alternate 1 ARHGAP23 36622550 chr2: 10902450-10904150 Gain Alternate 1 ATP6V1C2 chr7: 70060000-70066050 Gain Alternate 1 AUTS2 chr18: 60804550- Loss Alternate 1 BCL2 60807050 chr11: 1463100-1464700 Gain Alternate 1 BRSK2 chr4: 2038150-2039400 Gain Alternate 1 C4orf48 chr21: 44482600- Gain Alternate 1 CBS 44484300 chr3: 46988600-46990000 Gain Alternate 1 CCDC12 chr16: 28946800- Gain Alternate 1 CD19 28948350 chr6: 4836100-4837550 Gain Alternate 1 CDYL chr6: 118985250- Loss Alternate 1 CEP85L 118986450 chr9: 124497650- Gain Alternate 1 DAB2IP 124504300 chr19: 6474700-6477300 Gain Alternate 1 DENND1C chr4: 955250-957700 Gain Alternate 1 DGKQ chr16: 21059250- Gain Alternate 1 DNAH3 21060650 chr7: 35074250-35076850 Gain Alternate 1 DPY19L1 chr6: 56553350-56559100 Gain Alternate 1 DST chr2: 47595450-47602500 Gain Alternate 1 EPCAM chrX: 137860100- Gain Alternate 1 FGF13 137861300 chr3: 69283500-69286950 Gain Alternate 1 FRMD4B chr7: 99774000-99776200 Gain Alternate 1 GPC2 chr10: 25754300- Gain Alternate 1 GPR158 25755900 chr11: 123458150- Gain Alternate 1 GRAMD1B 123465950 chr20: 43029650- Gain Alternate 1 HNF4A 43032200 chr17: 46639600- Gain Alternate 1 HOXB3 46642950 chr7: 23506000-23515500 Gain Alternate 1 IGF2BP3 chr1: 38410700-38414500 Loss Alternate 1 INPP5B chr19: 17952000- Gain Alternate 1 JAK3 17953950 chr14: 24891600- Loss Alternate 1 KHNYN 24897600 chr18: 21452050- Gain Alternate 1 LAMA3 21455250 chr5: 154091500- Loss Alternate 1 LARP1 154095100 chr5: 38605950-38609550 Loss Alternate 1 LIFR chr16: 1013250-1015550 Gain Alternate 1 LMF1 chr19: 49003900- Gain Alternate 1 LMTK3 49005550 chr1: 156896950- Gain Alternate 1 LRRC71 156898350 chr1: 156893100- Gain Alternate 1 LRRC71 156894550 chr1: 236045300- Loss Alternate 1 LYST 236047550 chr20: 33134200- Gain Alternate 1 MAP1LC3A 33135900 chr7: 130125100- Gain Alternate 1 MEST 130127800 chr7: 116363550- Gain Alternate 1 MET 116365500 chr3: 158448250- Gain Alternate 1 MFSD1 158451400 chr1: 1562700-1565700 Gain Alternate 1 MIB2 chr14: 102700300- Gain Alternate 1 MOK 102702150 chr17: 60756900- Gain Alternate 1 MRC2 60758850 chr8: 144652950- Gain Alternate 1 MROH6 144655550 chr7: 100607850- Gain Alternate 1 MUC12 100613600 chr11: 76902300- Gain Alternate 1 MYO7A 76903800 chr1: 24434350-24435800 Gain Alternate 1 MYOM3 chr6: 126136250- Loss Alternate 1 NCOA7 126140700 chr2: 233755200- Gain Alternate 1 NGEF 233756650 chr2: 233791350- Gain Alternate 1 NGEF 233792700 chr17: 26119900- Gain Alternate 1 NOS2 26121850 chr1: 200007500- Gain Alternate 1 NR5A2 200010950 chr18: 55099800- Gain Alternate 1 ONECUT2 55108900 chr8: 107629450- Loss Alternate 1 OXR1 107632850 chr4: 169575100- Loss Alternate 1 PALLD 169577200 chr19: 18364400- Loss Alternate 1 PDE4C 18366800 chr4: 111557000- Gain Alternate 1 PITX2 111559350 chr8: 145009000- Gain Alternate 1 PLEC 145018500 chr19: 49370000- Gain Alternate 1 PLEKHA4 49372300 chr11: 16944700- Gain Alternate 1 PLEKHA7 16947800 chr1: 6530450-6535000 Gain Alternate 1 PLEKHG5 chr5: 74990850-74992350 Gain Alternate 1 POC5 chr6: 35359200-35364100 Loss Alternate 1 PPARD chr19: 49631500- Gain Alternate 1 PPFIA3 49632100 chr22: 22900650- Gain Alternate 1 PRAME 22902550 chr9: 132458700- Gain Alternate 1 PRRX2 132461300 chr9: 139873000- Gain Alternate 1 PTGDS 139874300 chr1: 29562850-29565950 Gain Alternate 1 PTPRU chr17: 2878500-2880550 Gain Alternate 1 RAP1GAP2 chr9: 134548500- Loss Alternate 1 RAPGEF1 134553400 chr3: 24851300-24854350 Loss Alternate 1 RARB chr13: 114769100- Gain Alternate 1 RASA3 114771100 chr20: 399750-402500 Gain Alternate 1 RBCK1 chr19: 14088450- Gain Alternate 1 RFX1 14090950 chr4: 3310150-3312100 Gain Alternate 1 RGS12 chr8: 74035400-74036300 Loss Alternate 1 SBSPON chr21: 38063750- Loss Alternate 1 SIM2 38066650 chr19: 19215350- Gain Alternate 1 SLC25A42 19217300 chr7: 103021250- Loss Alternate 1 SLC26A5 103022850 chr12: 40425950- Loss Alternate 1 SLC2A13 40427700 chr12: 20975550- Gain Alternate 1 SLCO1B3 20976900 chr16: 68418000- Loss Alternate 1 SMPD3 68421750 chr4: 186729400- Loss Alternate 1 SORBS2 186734150 chr2: 231206350- Gain Alternate 1 SP140L 231208750 chr7: 87854350-87856200 Gain Alternate 1 SRI chr3: 17734300-17735900 Gain Alternate 1 TBC1D5 chr8: 67866500-67867950 Gain Alternate 1 TCF24 chr6: 10409250-10419650 Gain Alternate 1 TFAP2A chr3: 129512300- Gain Alternate 1 TMCC1 129514550 chr18: 20910450- Gain Alternate 1 TMEM241 20912050 chr2: 218874000- Gain Alternate 1 TNS1 218875450 chr8: 141017700- Gain Alternate 1 TRAPPC9 141019200 chr4: 8435700-8439650 Loss Alternate 1 TRMT44 chr21: 45844650- Gain Alternate 1 TRPM2 45846700 chrX: 107016000- Loss Alternate 1 TSC22D3 107021000 chr2: 3371900-3374350 Gain Alternate 1 TSSC1 chr17: 40784750- Loss Alternate 1 TUBG2 40786950 chr16: 1428050-1430700 Gain Alternate 1 UNKL chr12: 109507100- Gain Alternate 1 USP30 109508350 chr20: 50719850- Gain Alternate 1 ZFP64 50723350 chr4: 8128400-8130450 Gain Alternate 0 ABLIM2 chr16: 72660100- Gain Alternate 0 AC004158.2 72662050 chr2: 66801200-66811950 Gain Alternate 0 AC007392.3 chr2: 114081700- Gain Alternate 0 AC016745.3 114084050 chr19: 52104750- Loss Alternate 0 AC018755.16 52106000 chr2: 19504600-19506400 Gain Alternate 0 AC092594.1 chr2: 118899750- Gain Alternate 0 AC093901.1 118901550 chr17: 263900-267650 Loss Alternate 0 AC108004.3 chr3: 18734950-18736300 Gain Alternate 0 AC144521.1 chr12: 109568950- Loss Alternate 0 ACACB 109570000 chrX: 23783150- Gain Alternate 0 ACOT9 23786000 chr7: 5601050-5603800 Gain Alternate 0 ACTB chr7: 15600650- Gain Alternate 0 AGMO 15602200 chr21: 45336050- Loss Alternate 0 AGPAT3 45337600 chr15: 86232000- Loss Alternate 0 AKAP13 86236800 chr9: 112909300- Loss Alternate 0 AKAP2 112915400 chr2: 241496150- Gain Alternate 0 ANKMY1 241498200 chr2: 242127000- Loss Alternate 0 ANO7 242129850 chr5: 139972550- Gain Alternate 0 APBB3 139973900 chr18: 24443050- Loss Alternate 0 AQP4-AS1 24445900 chr4: 86395150-86399900 Loss Alternate 0 ARHGAP24 chr19: 47362700- Gain Alternate 0 ARHGAP35 47367650 chr9: 35672750-35677150 Loss Alternate 0 ARHGEF39 chrX: 100739600- Gain Alternate 0 ARMCX4 100741600 chr9: 120175650- Loss Alternate 0 ASTN2 120177900 chr3: 193270000- Loss Alternate 0 ATP13A4 193274550 chr18: 77102950- Loss Alternate 0 ATP9B 77104300 chr1: 179486050- Loss Alternate 0 AXDND1 179487950 chr4: 102332100- Gain Alternate 0 BANK1 102333250 chr1: 94046300-94051100 Loss Alternate 0 BCAR3 chr11: 27686500- Gain Alternate 0 BDNF-AS 27687900 chr20: 11897750- Loss Alternate 0 BTBD3 11902000 chr11: 63531650- Gain Alternate 0 C11orf95 63533550 chr19: 30199050- Gain Alternate 0 C19orf12 30200500 chr1: 207991400- Loss Alternate 0 C1orf132 208001200 chr6: 109571700- Gain Alternate 0 C6orf183 109573350 chr8: 128305850- Gain Alternate 0 CASC8 128307550 chr5: 43409150-43412850 Loss Alternate 0 CCL28 chr8: 95245700-95247400 Gain Alternate 0 CDH17 chr7: 105603300- Loss Alternate 0 CDHR3 105604700 chr7: 90338500-90340500 Loss Alternate 0 CDK14 chr7: 29184550-29187650 Gain Alternate 0 CHN2 chr15: 79011600- Gain Alternate 0 CHRNB4 79013200 chr7: 139226300- Gain Alternate 0 CLEC2L 139228850 chr6: 25164900-25167200 Loss Alternate 0 CMAHP chr16: 81684900- Loss Alternate 0 CMIP 81687600 chr6: 37391200-37392800 Gain Alternate 0 CMTR1 chr3: 74662150-74664400 Loss Alternate 0 CNTN3 chr11: 111172600- Loss Alternate 0 COLCA1 111176650 chr6: 36722500-36725900 Loss Alternate 0 CPNE5 chr11: 85392850- Loss Alternate 0 CREBZF 85394650 chr16: 21288600- Gain Alternate 0 CRYM 21290700 chr5: 60597450-60601050 Loss Alternate 0 CTC- 436P18.3 chr15: 45544050- Loss Alternate 0 CTD- 45548600 2651B20.3 chr20: 110300-111350 Gain Alternate 0 DEFB126 chr2: 234326350- Loss Alternate 0 DGKD 234331500 chr1: 223101350- Loss Alternate 0 DISP1 223104800 chr11: 111852050- Loss Alternate 0 DIXDC1 111855050 chr13: 50759600- Gain Alternate 0 DLEU1 50762100 chr1: 46954600-46956800 Gain Alternate 0 DMBX1 chr16: 30021900- Gain Alternate 0 DOC2A 30023950 chr6: 56715250-56717500 Gain Alternate 0 DST chr18: 46894350- Loss Alternate 0 DYM 46895900 chr5: 106838450- Loss Alternate 0 EFNA5 106842400 chr4: 111331750- Gain Alternate 0 ENPEP 111333350 chr14: 74461400- Loss Alternate 0 ENTPD5 74463450 chr19: 55590850- Gain Alternate 0 EPS8L1 55593800 chr5: 172332450- Loss Alternate 0 ERGIC1 172333000 chr1: 17024500-17028900 Gain Alternate 0 ESPNP chr1: 216892850- Loss Alternate 0 ESRRG 216898200 chr1: 217249050- Loss Alternate 0 ESRRG 217252200 chr6: 36326200-36331550 Gain Alternate 0 ETV7 chr12: 124778800- Loss Alternate 0 FAM101A 124786100 chr17: 47822200- Loss Alternate 0 FAM117A 47825200 chr4: 187025100- Loss Alternate 0 FAM149A 187028650 chr1: 178986050- Loss Alternate 0 FAM20B 178987900 chr7: 102574000- Loss Alternate 0 FBXL13 102576900 chr16: 86529000- Loss Alternate 0 FENDRR 86534050 chr20: 34192700- Loss Alternate 0 FER1L4 34196000 chr8: 124926550- Gain Alternate 0 FER1L6 124929550 chr7: 121942750- Gain Alternate 0 FEZF1 121947900 chr12: 32654200- Loss Alternate 0 FGD4 32659150 chr16: 86608950- Gain Alternate 0 FOXL1 86611800 chr8: 75230900-75235150 Gain Alternate 0 GDAP1 chr7: 100288750- Gain Alternate 0 GIGYF1 100293000 chr11: 58694450- Loss Alternate 0 GLYATL1 58696550 chr5: 89854500-89855350 Loss Alternate 0 GPR98 chr2: 165476750- Gain Alternate 0 GRB14 165479250 chr9: 140056700- Gain Alternate 0 GRIN1 140058300 chr19: 48900250- Gain Alternate 0 GRIN2D 48904400 chr9: 104466750- Gain Alternate 0 GRIN3A 104468450 chr3: 14642850-14644150 Loss Alternate 0 GRIP2 chr11: 2016000-2021350 Gain Alternate 0 H19 chrX: 152760450- Gain Alternate 0 HAUS7 152761150 chr7: 18534500-18539050 Loss Alternate 0 HDAC9 chr15: 83619150- Loss Alternate 0 HOMER2 83622750 chr7: 27159450-27164850 Gain Alternate 0 HOXA3 chr7: 27208400-27220700 Gain Alternate 0 HOXA9 chr17: 46678350- Gain Alternate 0 HOXB6 46683450 chr17: 46694850- Gain Alternate 0 HOXB8 46697150 chr3: 11178050-11179900 Gain Alternate 0 HRH1 chr3: 11195250-11198600 Gain Alternate 0 HRH1 chr3: 11265900-11269000 Gain Alternate 0 HRH1 chr1: 23543800-23544900 Gain Alternate 0 HTR1D chrX: 130711450- Gain Alternate 0 IGSF1 130713600 chr17: 38016450- Loss Alternate 0 IKZF3 38022250 chr2: 113619100- Loss Alternate 0 IL1B 113622250 chr4: 143394250- Gain Alternate 0 INPP4B 143396200 chr19: 2255550-2257400 Loss Alternate 0 JSRP1 chr17: 68071050- Loss Alternate 0 KCNJ16 68073700 chr14: 88788450- Gain Alternate 0 KCNK10 88791000 chr4: 56914350-56916700 Gain Alternate 0 KIAA1211 chr10: 24725650- Loss Alternate 0 KIAA1217 24728200 chr11: 33398050- Gain Alternate 0 KIAA1549L 33400750 chr15: 31637200- Loss Alternate 0 KLF13 31640250 chr19: 55019200- Gain Alternate 0 LAIR2 55020400 chr1: 65991250-65992850 Loss Alternate 0 LEPR chr5: 78014050-78017100 Loss Alternate 0 LHFPL2 chr12: 113904650- Gain Alternate 0 LHX5 113906650 chr22: 30651400- Gain Alternate 0 LIF 30654850 chr20: 21085550- Gain Alternate 0 LINC00237 21087550 chr13: 74234250- Gain Alternate 0 LINC00393 74236800 chr3: 8652200-8654000 Gain Alternate 0 LMCD1- AS1 chr20: 6031700-6033850 Gain Alternate 0 LRRN4 chr3: 116161150- Gain Alternate 0 LSAMP 116164900 chr11: 1889150-1894600 Loss Alternate 0 LSP1 chrX: 149588950- Gain Alternate 0 MAMLD1 149590100 chr1: 27683050-27684600 Loss Alternate 0 MAP3K6 chrX: 20115700- Loss Alternate 0 MAP7D2 20118300 chr3: 150959500- Gain Alternate 0 MED12L 150960300 chr22: 42148300- Loss Alternate 0 MEI1 42150300 chr1: 205537050- Loss Alternate 0 MFSD4 205540700 chr1: 22489600-22491100 Gain Alternate 0 MIR4418 chr19: 748150-750100 Gain Alternate 0 MISP chr3: 69914350-69917750 Loss Alternate 0 MITF chr6: 168215700- Gain Alternate 0 MLLT4- 168217350 AS1 chr19: 1286150-1288700 Gain Alternate 0 MUM1 chr19: 50690700- Gain Alternate 0 MYH14 50695700 chr17: 73606350- Gain Alternate 0 MYO156 73609450 chr17: 31010250- Gain Alternate 0 MYO1D 31012000 chr18: 55888350- Loss Alternate 0 NEDD4L 55892150 chr2: 131965200- Gain Alternate 0 NF1P8 131968600 chr14: 27147750- Gain Alternate 0 NOVA1- 27148900 AS1 chr11: 108040050- Loss Alternate 0 NPAT 108041550 chr7: 98248450-98250250 Gain Alternate 0 NPTX2 chr15: 76302650- Loss Alternate 0 NRG4 76305350 chr9: 132370500- Gain Alternate 0 NTMT1 132373750 chr3: 32118200-32120100 Gain Alternate 0 OSBPL10 chr19: 14171500- Loss Alternate 0 PALM3 14173250 chr7: 32107350-32111900 Loss Alternate 0 PDE1C chr3: 111450850- Loss Alternate 0 PHLDB2 111453300 chr12: 18395250- Loss Alternate 0 PIK3C2G 18399450 chr8: 110534900- Loss Alternate 0 PKHD1L1 110536100 chr20: 8094750-8096650 Gain Alternate 0 PLCB1 chr1: 6544500-6545600 Gain Alternate 0 PLEKHG5 chr22: 41990400- Gain Alternate 0 PMM1 41991450 chr6: 31150550-31154950 Loss Alternate 0 POU5F1 chr11: 7626600-7631400 Loss Alternate 0 PPFIBP2 chr2: 182895050- Gain Alternate 0 PPP1R1C 182896750 chr8: 143759850- Loss Alternate 0 PSCA 143765700 chr8: 27237450-27239750 Loss Alternate 0 PTK2B chr8: 142384050- Gain Alternate 0 PTP4A3 142385550 chr9: 96767600-96770450 Loss Alternate 0 PTPDC1 chr12: 120661250- Loss Alternate 0 PXN 120664850 chr18: 52384600- Loss Alternate 0 RAB27B 52386250 chr11: 82706750- Loss Alternate 0 RAB30 82709350 chr8: 95485350-95488300 Gain Alternate 0 RAD54B chr4: 82964050-82966400 Gain Alternate 0 RASGEF1B chr4: 40512300-40518850 Loss Alternate 0 RBM47 chr9: 116225550- Gain Alternate 0 RGS3 116228700 chr10: 62758000- Loss Alternate 0 RHOBTB1 62762450 chr8: 104510350- Gain Alternate 0 RIMS2 104514700 chr21: 38379100- Gain Alternate 0 RIPPLY3 38379750 chr8: 61324800-61327100 Gain Alternate 0 RP11- 163N6.2 chr20: 6301750-6304300 Gain Alternate 0 RP11- 199O14.1 chr3: 187606800- Gain Alternate 0 RP11- 187608950 30O15.1 chr1: 39191950-39194400 Loss Alternate 0 RP11- 334L9.1 chr11: 112140350- Gain Alternate 0 RP11- 112142500 356J5.12 chr6: 82809950-82812100 Gain Alternate 0 RP11- 379B8.1 chr14: 39702300- Loss Alternate 0 RP11- 39706400 407N17.3 chr1: 203394800- Gain Alternate 0 RP11- 203398950 435P24.3 chr9: 72091300-72092650 Gain Alternate 0 RP11- 470P21.2 chr15: 82161650- Gain Alternate 0 RP11- 82163400 499F3.2 chr4: 88631250- Gain Alternate 0 RP11- 88631950 742B18.1 chr11: 94372300- Gain Alternate 0 RP11- 94374550 867G2.5 chr3: 131049650- Gain Alternate 0 RP11- 131051500 933H2.4 chr17: 10746250- Loss Alternate 0 RP11- 10749200 963H4.3 chr6: 85334900-85337050 Gain Alternate 0 RP1- 90L14.1 chr7: 156735150- Gain Alternate 0 RP5- 156736500 1121A15.3 chr2: 55236200-55238400 Loss Alternate 0 RTN4 chr16: 51186150- Loss Alternate 0 SALL1 51187850 chr2: 200326950- Gain Alternate 0 SATB2 200329550 chr3: 53031650-53034600 Gain Alternate 0 SFMBT1 chr14: 71849000- Loss Alternate 0 SIPA1L1 71850350 chr1: 232760700- Gain Alternate 0 SIPA1L2 232767700 chr7: 100448750- Gain Alternate 0 SLC12A9 100451750 chr12: 105344050- Loss Alternate 0 SLC41A2 105348050 chr6: 31843950-31847850 Loss Alternate 0 SLC44A4 chr1: 75840850-75842350 Gain Alternate 0 SLC44A5 chr1: 205637750- Gain Alternate 0 SLC45A3 205639250 chr11: 26985950- Gain Alternate 0 SLC5A12 26987450 chr14: 23622000- Loss Alternate 0 SLC7A8 23623950 chr22: 31459200- Gain Alternate 0 SMTN 31461650 chr20: 10197250- Gain Alternate 0 SNAP25- 10201300 AS1 chr16: 1842850-1844950 Loss Alternate 0 SPSB3 chr11: 4010850-4011700 Loss Alternate 0 STIM1 chr8: 99951150-99961750 Gain Alternate 0 STK3 chr7: 23761400-23764000 Gain Alternate 0 STK31 chr1: 110573450- Loss Alternate 0 STRIP1 110574700 chr7: 73131100-73134700 Gain Alternate 0 STX1A chr20: 46411750- Gain Alternate 0 SULF2 46414250 chr12: 79438650- Gain Alternate 0 SYT1 79440250 chr15: 57509850- Loss Alternate 0 TCF12 57515600 chr12: 110411050- Gain Alternate 0 TCHP 110419200 chr21: 32640100- Loss Alternate 0 TIAM1 32641350 chr19: 3707600-3711250 Loss Alternate 0 TJP3 chr10: 102830000- Loss Alternate 0 TLX1NB 102833650 chr2: 228241600- Gain Alternate 0 TM4SF20 228244450 chr16: 19427700- Gain Alternate 0 TMC5 19435900 chr7: 47490900-47493500 Loss Alternate 0 TNS3 chr8: 144436800- Gain Alternate 0 TOP1MT 144438000 chr13: 45955000- Gain Alternate 0 TPT1-AS1 45957700 chr17: 3459750-3462900 Loss Alternate 0 TRPV3 chr3: 12522200-12524700 Gain Alternate 0 TSEN2 chr22: 46683150- Loss Alternate 0 TTC38 46685350 chr6: 133003800- Gain Alternate 0 VNN1 133008900 chr15: 53831700- Gain Alternate 0 WDR72 53833550 chr11: 102617350- Gain Alternate 0 WTAPP1 102619450 chr11: 68436350- Gain Alternate 0 Novel Gene 68438200 chr12: 125226400- Loss Alternate 0 Novel Gene 125228400 chr12: 89240400- Gain Alternate 0 Novel Gene 89241750 chr14: 99752650- Loss Alternate 0 Novel Gene 99754000 chr18: 76805850- Gain Alternate 0 Novel Gene 76809250 chr19: 53560600- Gain Alternate 0 Novel Gene 53562700 chr2: 45227500-45229600 Gain Alternate 0 Novel Gene chr2: 134784950- Gain Alternate 0 Novel Gene 134786450 chr2: 176458500- Gain Alternate 0 Novel Gene 176460750 chr20: 46600150- Gain Alternate 0 Novel Gene 46603250 chr4: 10830100-10832350 Gain Alternate 0 Novel Gene chr5: 35404300-35405800 Gain Alternate 0 Novel Gene chr5: 42999400-43001150 Gain Alternate 0 Novel Gene chr5: 72496650-72498300 Gain Alternate 0 Novel Gene chr1: 204682350- Loss Alternate 0 Novel Gene 204684550 chr6: 868400-871100 Loss Alternate 0 Novel Gene chr1: 220635500- Gain Alternate 0 Novel Gene 220637400 chr6: 47146850-47150550 Loss Alternate 0 Novel Gene chr6: 160720200- Gain Alternate 0 Novel Gene 160722150 chr6: 170474550- Gain Alternate 0 Novel Gene 170475800 chr1: 242107250- Gain Alternate 0 Novel Gene 242109450 chr7: 27274550-27276500 Gain Alternate 0 Novel Gene chr9: 17905350-17908250 Loss Alternate 0 Novel Gene chr9: 31848250-31849950 Gain Alternate 0 Novel Gene chrX: 56133300- Gain Alternate 0 Novel Gene 56134800 chrX: 3466450-3468750 Gain Alternate 0 Novel Gene chrX: 6849150-6851300 Gain Alternate 0 Novel Gene chr11: 60941900- Loss Alternate 0 Novel Gene 60945700 chr11: 71350450- Gain Alternate 0 Novel Gene 71351500 chr11: 119775600- Loss Alternate 0 Novel Gene 119779600 chr5: 82391600-82392950 Gain Alternate 0 XRCC4 chr3: 141107100- Loss Alternate 0 ZBTB38 141108400 chr18: 45660800- Loss Alternate 0 ZBTB7C 45664950 chr13: 100619800- Gain Alternate 0 ZIC5 100623100 chr2: 180425300- Loss Alternate 0 ZNF385B 180426950 chr19: 53539900- Gain Alternate 0 ZNF702P 53541600

To explore the influence of alternative promoters on protein diversity, we identified 714 tumor-specific promoter alterations predicted to change N-terminal protein composition and also supported by both H3K4me3 and RNA-seq data. The vast majority of these alterations (>95%) were in-frame to that of the canonical protein. Of these, 47% (n=338) were predicted to cause gains of new N-terminal peptides in tumors (see Methods). To confirm protein-level expression of these N-terminal peptides in gastrointestinal cancer, we queried publically available peptide spectral data of 90 TCGA colorectal cancer (CRC) and 60 normal colon samples. CRC data was used for this analysis as large-scale proteomic data of primary GCs are not currently available, and because many GC somatic promoters are also observed in CRC (FIG. 2d ). Among N-terminal peptides predicted to be gained in tumors, we confirmed protein expression of 33% (112/338) in the CRC data (Table 7), of which 51.8% were overexpressed in CRC samples relative to normal colon samples (FDR 10%). In a separate experiment, we further investigated if these N-terminal peptides also exhibit tumor overexpression in proteomic data from 3 GC cell lines and 1 normal gastric epithelial line (GES1) (Methods and Materials). Similar to the CRC data, 48% of the N-terminal peptides were overexpressed in the GC lines relative to normal GES1 gastric cells. Taken collectively, these analyses suggest that alternative promoters may contribute significantly towards proteomic diversity in gastrointestinal cancer.

TABLE 7 Spectral Counts from CRC samples of N terminal peptides predicted to be gained in GC Spectral SEQ_ID_NO Peptide GeneId Count SEQ ID NO: 1 IDNSQVESGSLEDDWDFLPPKK ENSG00000179218.9 2602 SEQ ID NO: 2 FYALSASFEPFSNK ENSG00000179218.9 2047 SEQ ID NO: 3 EQFLDGDGWTSR ENSG00000179218.9 1370 SEQ ID NO: 4 IKDPDASKPEDWDER ENSG00000179218.9 805 SEQ ID NO: 5 GDVTAQIALQPALK ENSG00000112096.12 601 SEQ ID NO: 6 GISLNPEQWSQLK ENSG00000113387.7 536 SEQ ID NO: 7 AYHSFLVEPISCHAWNK ENSG00000130429.8 497 SEQ ID NO: 8 IAVQPGTVGPQGR ENSG00000134871.13 468 SEQ ID NO: 9 VLAQNSGFDLQETLVK ENSG00000146731.6 435 SEQ ID NO: 10 CKDDEFTHLYTLIVRPDNTYEVK ENSG00000179218.9 424 SEQ ID NO: 11 AKIDDPTDSKPEDWDKPEHIPDP ENSG00000179218.9 414 DAK SEQ ID NO: 12 VHVIFNYK ENSG00000179218.9 396 SEQ ID NO: 13 HEQNIDCGGGYVK ENSG00000179218.9 361 SEQ ID NO: 14 LIDFGLAR ENSG00000065534.14 359 SEQ ID NO: 15 TWKPTLVILR ENSG00000130429.8 358 SEQ ID NO: 16 AIWNVINWENVTER ENSG00000112096.12 353 SEQ ID NO: 17 IDDPTDSKPEDWDKPEHIPDPDA ENSG00000179218.9 323 K SEQ ID NO: 18 NVRPDYLK ENSG00000112096.12 320 SEQ ID NO: 19 NSVSQISVLSGGK ENSG00000130429.8 317 SEQ ID NO: 20 DGNVLLHEMQIQHPTASLIAK ENSG00000146731.6 314 SEQ ID NO: 21 AGATHVER ENSG00000145016.9 311 SEQ ID NO: 22 LVALLNTLDR ENSG00000119383.15 298 SEQ ID NO: 23 HHAAYVNNLNVTEEK ENSG00000112096.12 296 SEQ ID NO: 24 FYGDEEKDKGLQTSQDAR ENSG00000179218.9 290 SEQ ID NO: 25 KVHVIFNYK ENSG00000179218.9 283 SEQ ID NO: 26 GPLPAAPPVAPER ENSG00000115310.13 282 SEQ ID NO: 27 VLLSALER ENSG00000100714.11 277 SEQ ID NO: 28 SVSIGYLLVK ENSG00000134871.13 276 SEQ ID NO: 29 IQQEIAVQNPLVSER ENSG00000167770.7 271 SEQ ID NO: 30 GELLEAIKR ENSG00000112096.12 268 SEQ ID NO: 31 AHNQDLGLAGSCLAR ENSG00000134871.13 265 SEQ ID NO: 32 YVVVTGITPTPLGEGK ENSG00000100714.11 256 SEQ ID NO: 33 MEDLDQSPLVSSSDSPPRPQPAF ENSG00000115310.13 254 K SEQ ID NO: 34 AAQAPSSFQLLYDLK ENSG00000100714.11 253 SEQ ID NO: 35 LQAQLNELQAQLSQK ENSG00000137497.13 250 SEQ ID NO: 36 ALQFLEEVK ENSG00000146731.6 244 SEQ ID NO: 37 LLTSGYLQR ENSG00000167770.7 242 SEQ ID NO: 38 GDLNDCFIPCTPK ENSG00000100714.11 241 SEQ ID NO: 39 ASSEGGTAAGAGLDSLHK ENSG00000130429.8 240 SEQ ID NO: 40 EAVTEILGIEPDREK ENSG00000211460.7 236 SEQ ID NO: 41 EVEERPAPTPWGSK ENSG00000130429.8 235 SEQ ID NO: 42 IITEGFEAAK ENSG00000146731.6 235 SEQ ID NO: 43 YLNIFGESQPNPK ENSG00000004864.9 234 SEQ ID NO: 44 LTAASVGVQGSGWGWLGFNK ENSG00000112096.12 229 SEQ ID NO: 45 IAPLEEGTLPFNLAEAQR ENSG00000004864.9 221 SEQ ID NO: 46 GQTLVVQFTVK ENSG00000179218.9 220 SEQ ID NO: 47 AQLGVQAFADALLIIPK ENSG00000146731.6 217 SEQ ID NO: 48 QVAPEKPVK ENSG00000113387.7 217 SEQ ID NO: 49 VATAQDDITGDGTTSNVLIIGELL ENSG00000146731.6 215 K SEQ ID NO: 50 GLLPQLLGVAPEK ENSG00000004864.9 214 SEQ ID NO: 51 NAYVWTLK ENSG00000130429.8 214 SEQ ID NO: 52 IYGADDIELLPEAQHK ENSG00000100714.11 211 SEQ ID NO: 53 CHAIIDEQPLIFK ENSG00000169756.12 210 SEQ ID NO: 54 KGISLNPEQWSQLK ENSG00000113387.7 209 SEQ ID NO: 55 GIDPFSLDALSK ENSG00000146731.6 207 SEQ ID NO: 56 LLQCYPPPEDAAVK ENSG00000196961.8 207 SEQ ID NO: 57 GVPTGFILPIR ENSG00000100714.11 204 SEQ ID NO: 58 IVTCGTDR ENSG00000130429.8 204 SEQ ID NO: 59 TPVPSDIDISR ENSG00000100714.11 203 SEQ ID NO: 60 YQEALAK ENSG00000112096.12 198 SEQ ID NO: 61 VAWVSHDSTVCLADADKK ENSG00000130429.8 197 SEQ ID NO: 62 LDIDPETITWQR ENSG00000100714.11 194 SEQ ID NO: 63 IDNSQVESGSLEDDWDFLPPK ENSG00000179218.9 192 SEQ ID NO: 64 LAILQVGNR ENSG00000100714.11 192 SEQ ID NO: 65 AQAALAVNISAAR ENSG00000146731.6 191 SEQ ID NO: 66 GALALAQAVQR ENSG00000100714.11 189 SEQ ID NO: 67 TDPTTLTDEEINR ENSG00000100714.11 189 SEQ ID NO: 68 LELSVLYK ENSG00000167770.7 188 SEQ ID NO: 69 GLDGYQGPDGPR ENSG00000134871.13 187 SEQ ID NO: 70 LSGLEQPQGALQTR ENSG00000133316.11 184 SEQ ID NO: 71 SCQTALVEILDVIVR ENSG00000067704.8 182 SEQ ID NO: 72 DDNMFQIGK ENSG00000113387.7 181 SEQ ID NO: 73 EHNGQVTGIDWAPESNR ENSG00000130429.8 179 SEQ ID NO: 74 KIKDPDASKPEDWDER ENSG00000179218.9 178 SEQ ID NO: 75 MFGIPVVVAVNAFK ENSG00000100714.11 178 SEQ ID NO: 76 FFEHFIEGGR ENSG00000167770.7 177 SEQ ID NO: 77 IFHELTQTDK ENSG00000100714.11 174 SEQ ID NO: 78 FINLFPETK ENSG00000196961.8 172 SEQ ID NO: 79 FYGDEEKDK ENSG00000179218.9 172 SEQ ID NO: 80 FNGGGHINHSIFWTNLSPNGGG ENSG00000112096.12 169 EPK SEQ ID NO: 81 DPDASKPEDWDER ENSG00000179218.9 168 SEQ ID NO: 82 LGSPDYGNSALLSLPGYRPTTR ENSG00000137497.13 168 SEQ ID NO: 83 ASGDSARPVLLQVAESAYR ENSG00000004864.9 167 SEQ ID NO: 84 TDTESELDLISR ENSG00000100714.11 166 SEQ ID NO: 85 LDFVCSFLQK ENSG00000137497.13 165 SEQ ID NO: 86 WIDETPPVDQPSR ENSG00000119383.15 165 SEQ ID NO: 87 GLLGALTSTPYSPTQHLER ENSG00000153310.14 164 SEQ ID NO: 88 KPEDWDEEMDGEWEPPVIQNP ENSG00000179218.9 162 EYK SEQ ID NO: 89 FSDIQIR ENSG00000100714.11 160 SEQ ID NO: 90 STSFNVQDLLPDHEYK ENSG00000065534.14 160 SEQ ID NO: 91 GEQGFMGNTGPTGAVGDR ENSG00000134871.13 159 SEQ ID NO: 92 QPSQGPTFGIK ENSG00000100714.11 157 SEQ ID NO: 93 THLSLSHNPEQK ENSG00000100714.11 157 SEQ ID NO: 94 APVPSTCSSTFPEELSPPSHQAK ENSG00000137497.13 155 SEQ ID NO: 95 GEGGTTNPHIFPEGSEPK ENSG00000167770.7 155 SEQ ID NO: 96 TALAEAELEYNPEHVSR ENSG00000067704.8 155 SEQ ID NO: 97 FPLLKPSPK ENSG00000067704.8 154 SEQ ID NO: 98 DQAANLMANR ENSG00000198947.10 153 SEQ ID NO: 99 HLTAQVR ENSG00000137497.13 153 SEQ ID NO: FVLSSGK ENSG00000179218.9 149 100 SEQ ID NO: SSLPPVLGTESDATVK ENSG00000065534.14 148 101 SEQ ID NO: AWGAVVPLVGK ENSG00000153310.14 146 102 SEQ ID NO: IEGYPDPEVVWFK ENSG00000065534.14 145 103 SEQ ID NO: GKNVLINK ENSG00000179218.9 144 104 SEQ ID NO: GLQTSQDAR ENSG00000179218.9 144 105 SEQ ID NO: HTLTQIK ENSG00000146731.6 144 106 SEQ ID NO: VHAELADVLTEAVVDSILAIK ENSG00000146731.6 144 107 SEQ ID NO: YVIHTVGPIAYGEPSASQAAELR ENSG00000133315.6 142 108 SEQ ID NO: IQSSHNFQLESVNK ENSG00000135052.12 141 109 SEQ ID NO: QIDNPDYK ENSG00000179218.9 140 110 SEQ ID NO: DAEGILEDLQSYR ENSG00000153310.14 139 111 SEQ ID NO: YTAESSDTLCPR ENSG00000067704.8 139 112 SEQ ID NO: EESREPAPASPAPAGVEIR ENSG00000113657.8 138 113 SEQ ID NO: EMDRETLIDVAR ENSG00000146731.6 138 114 SEQ ID NO: NEVSFVIHNLPVLAK ENSG00000086475.10 138 115 SEQ ID NO: QVAPEKPVKK ENSG00000113387.7 137 116 SEQ ID NO: FLINLEGGDIR ENSG00000067704.8 136 117 SEQ ID NO: LSVNSVTAGDYSR ENSG00000211460.7 135 118 SEQ ID NO: QAQVNLTVVDKPDPPAGTPCAS ENSG00000065534.14 135 119 DIR SEQ ID NO: IFDDVSSGVSQLASK ENSG00000101199.8 134 120 SEQ ID NO: PDASKPEDWDER ENSG00000179218.9 134 121 SEQ ID NO: YGGAPQALTLK ENSG00000196961.8 132 122 SEQ ID NO: LVTPGETPSWTGSGFVR ENSG00000172037.9 131 123 SEQ ID NO: EQISDIDDAVR ENSG00000113387.7 129 124 SEQ ID NO: KPAAGLSAAPVPTAPAAGAPLM ENSG00000115310.13 129 125 DFGNDFVPPAPR SEQ ID NO: ATSSTQSLAR ENSG00000137497.13 128 126 SEQ ID NO: LLVPTQFVGAIIGK ENSG00000136231.9 128 127 SEQ ID NO: GELLEAIK ENSG00000112096.12 126 128 SEQ ID NO: FFQPTEMAAQDFFQR ENSG00000196961.8 124 129 SEQ ID NO: GSGSRPGIEGDTPR ENSG00000113657.8 121 130 SEQ ID NO: NAIDDGCVVPGAGAVEVAMAE ENSG00000146731.6 121 131 ALIK SEQ ID NO: AAAAAAVGPGAGGAGSAVPGG ENSG00000142453.7 120 132 AGPCATVSVFPGAR SEQ ID NO: DFLTPPLLSVR ENSG00000196961.8 120 133 SEQ ID NO: LFVVPADEAQAR ENSG00000105223.14 120 134 SEQ ID NO: WMIQYNNLNLK ENSG00000100714.11 120 135 SEQ ID NO: SLPISLVFLVPVR ENSG00000169896.12 119 136 SEQ ID NO: ALQVGCLLR ENSG00000196961.8 118 137 SEQ ID NO: ESFNPESYELDK ENSG00000086475.10 118 138 SEQ ID NO: TGWISTSSIWK ENSG00000067704.8 118 139 SEQ ID NO: EYAEDDNIYQQK ENSG00000167770.7 117 140 SEQ ID NO: TQIAICPNNHEVHIYEK ENSG00000130429.8 117 141 SEQ ID NO: SLEAQVAHADQQLR ENSG00000137497.13 116 142 SEQ ID NO: SVTLLIK ENSG00000146731.6 116 143 SEQ ID NO: IHFVPGWDCHGLPIEIK ENSG00000067704.8 115 144 SEQ ID NO: QQPDTELEIQQK ENSG00000067704.8 115 145 SEQ ID NO: KGEPVSAEDLGVSGALTVLMK ENSG00000100714.11 114 146 SEQ ID NO: LGIGMDTCVIPLR ENSG00000086475.10 113 147 SEQ ID NO: QPSWDPSPVSSTVPAPSPLSAAA ENSG00000115310.13 113 148 VSPSK SEQ ID NO: QISEGVEYIHK ENSG00000065534.14 109 149 SEQ ID NO: SEGGTAAGAGLDSLHK ENSG00000130429.8 108 150 SEQ ID NO: PTGFILPIR ENSG00000100714.11 107 151 SEQ ID NO: SQAGVSSGAPPGR ENSG00000137497.13 107 152 SEQ ID NO: VCGDSDKGFVVINQK ENSG00000146731.6 107 153 SEQ ID NO: LGIVQGIVGAR ENSG00000172037.9 104 154 SEQ ID NO: FLSLPEVR ENSG00000106066.9 103 155 SEQ ID NO: GLVLDHGAR ENSG00000146731.6 102 156 SEQ ID NO: LKNQVTQLK ENSG00000100714.11 102 157 SEQ ID NO: TSVQFQNFSPTVVHPGDLQTQL ENSG00000196961.8 102 158 AVQTK SEQ ID NO: EPPYGADVLR ENSG00000067704.8 101 159 SEQ ID NO: AAGPLLTDECR ENSG00000133315.6 100 160 SEQ ID NO: IIEVAPQVATQNVNPTPGATS ENSG00000086475.10 100 161 SEQ ID NO: LFSQGQDVSNK ENSG00000130396.16 100 162 SEQ ID NO: VSGPWEEADAEAVAR ENSG00000090006.13 100 163 SEQ ID NO: VTGTQPITCTWMK ENSG00000065534.14 100 164 SEQ ID NO: VLIDIR ENSG00000113387.7 99 165 SEQ ID NO: AVLEEGTDVVIK ENSG00000067704.8 98 166 SEQ ID NO: QFAEILHFTLR ENSG00000153310.14 97 167 SEQ ID NO: IVGAPMHDLLLWNNATVTTCHS ENSG00000100714.11 96 168 K SEQ ID NO: AYIQENLELVEK ENSG00000100714.11 95 169 SEQ ID NO: EIGLLSEEVELYGETK ENSG00000100714.11 95 170 SEQ ID NO: DSFLGSIPGK ENSG00000067704.8 94 171 SEQ ID NO: QLDALLEALK ENSG00000172037.9 94 172 SEQ ID NO: IIDEDFELTER ENSG00000065534.14 93 173 SEQ ID NO: DTINLLDQR ENSG00000135052.12 92 174 SEQ ID NO: VVQSLEQTAR ENSG00000211460.7 92 175 SEQ ID NO: DDSNLYINVK ENSG00000100714.11 90 176 SEQ ID NO: VSGQPQSVTASSDK ENSG00000101199.8 90 177 SEQ ID NO: EFCQQEVEPMCK ENSG00000167770.7 89 178 SEQ ID NO: AGNSLAASTAEETAGSAQGR ENSG00000172037.9 88 179 SEQ ID NO: EYWMDPEGEMKPGR ENSG00000113387.7 88 180 SEQ ID NO: LQSQLLSIEK ENSG00000106976.14 88 181 SEQ ID NO: AGESVELFGK ENSG00000065534.14 86 182 SEQ ID NO: NGEFFMSPNDFVTR ENSG00000004864.9 86 183 SEQ ID NO: VVVGAPQEIVAANQR ENSG00000169896.12 86 184 SEQ ID NO: SQAPLESSLDSLGDVFLDSGRK ENSG00000137497.13 85 185 SEQ ID NO: GCLELIK ENSG00000100714.11 84 186 SEQ ID NO: HSQTDQEPMCPVGMNK ENSG00000134871.13 84 187 SEQ ID NO: NPQVCGPGR ENSG00000090006.13 83 188 SEQ ID NO: SRGPGAPCQDVDECAR ENSG00000090006.13 83 189 SEQ ID NO: TKDEYLINSQTTEHIVK ENSG00000067704.8 83 190 SEQ ID NO: IATTTASAATAAAIGATPR ENSG00000137497.13 82 191 SEQ ID NO: LGHELQQAGLK ENSG00000137497.13 82 192 SEQ ID NO: TEVPPLLLILDR ENSG00000136631.8 82 193 SEQ ID NO: YGDEEKDK ENSG00000179218.9 82 194 SEQ ID NO: SESQGTAPAFK ENSG00000065534.14 81 195 SEQ ID NO: LPQEPGREQVVEDRPVGGR ENSG00000135052.12 80 196 SEQ ID NO: LPYGGQCRPCPCPEGPGSQR ENSG00000172037.9 79 197 SEQ ID NO: VYLLYRPGHYDILYK ENSG00000167770.7 79 198 SEQ ID NO: FQVATDALK ENSG00000137497.13 78 199 SEQ ID NO: LQEGQTLEFLVASVPK ENSG00000172037.9 78 200 SEQ ID NO: LQGAVCGVSSGPPPPR ENSG00000011028.9 78 201 SEQ ID NO: IQNVVTSFAPQR ENSG00000172037.9 77 202 SEQ ID NO: VSTLQNQR ENSG00000169896.12 77 203 SEQ ID NO: LSQLEEHLSQLQDNPPQEK ENSG00000137497.13 76 204 SEQ ID NO: SQAPLESSLDSLGDVFLDSGR ENSG00000137497.13 76 205 SEQ ID NO: AGPDLASCLDVDECR ENSG00000090006.13 75 206 SEQ ID NO: GTCHYYANK ENSG00000134871.13 74 207 SEQ ID NO: HKSETDTSLIR ENSG00000146731.6 74 208 SEQ ID NO: KQQNQELQEQLR ENSG00000137497.13 74 209 SEQ ID NO: SGDLYVLAADK ENSG00000067704.8 74 210 SEQ ID NO: AFGFSHLEALLDDSK ENSG00000167770.7 73 211 SEQ ID NO: EILTLLQGVHQGAGFQDIPK ENSG00000211460.7 73 212 SEQ ID NO: IQQCPGTETAEYQSLCPHGR ENSG00000090006.13 73 213 SEQ ID NO: KDPDASKPEDWDER ENSG00000179218.9 73 214 SEQ ID NO: SYWLSTTAPLPMMPVAEDEIKPY ENSG00000134871.13 73 215 ISR SEQ ID NO: VPQDVLQK ENSG00000086475.10 73 216 SEQ ID NO: DFGSFDKFK ENSG00000112096.12 72 217 SEQ ID NO: FIILSQEGSLCSVSIEK ENSG00000065534.14 72 218 SEQ ID NO: LAVATFAGIENK ENSG00000004864.9 72 219 SEQ ID NO: RLENAGSLK ENSG00000065534.14 72 220 SEQ ID NO: AAMPPQIIQFPEDQK ENSG00000065534.14 71 221 SEQ ID NO: EAQNLSAMEIR ENSG00000067704.8 71 222 SEQ ID NO: ILVAGDSMDSVK ENSG00000196961.8 71 223 SEQ ID NO: LVHSYPYDWR ENSG00000067704.8 71 224 SEQ ID NO: AEAGDAALSVAEWLR ENSG00000186635.10 70 225 SEQ ID NO: ELSNFYFSIIK ENSG00000067704.8 70 226 SEQ ID NO: AEAAAPYTVLAQSAPR ENSG00000090006.13 69 227 SEQ ID NO: GPGAPCQDVDECAR ENSG00000090006.13 69 228 SEQ ID NO: VSDFYDIEER ENSG00000065534.14 69 229 SEQ ID NO: NNDFYVTGESYAGK ENSG00000106066.9 68 230 SEQ ID NO: QPVVDTFDIR ENSG00000142453.7 68 231 SEQ ID NO: QQLQALSEPQPR ENSG00000135052.12 68 232 SEQ ID NO: APAEILNGKEISAQIR ENSG00000100714.11 67 233 SEQ ID NO: KLDVEEPDSANSSFYSTR ENSG00000137497.13 67 234 SEQ ID NO: QPPPDSSEEAPPATQNFIIPK ENSG00000119383.15 67 235 SEQ ID NO: SLADVDAILAR ENSG00000172037.9 67 236 SEQ ID NO: TGGSAQPETPYSGPGLLIDSLVLL ENSG00000172037.9 67 237 PR SEQ ID NO: CDLCQEVLADIGFVK ENSG00000169756.12 66 238 SEQ ID NO: FIAGTGCLVR ENSG00000184207.8 66 239 SEQ ID NO: HHAAYVNNLNVTEEKYQEALAK ENSG00000112096.12 66 240 SEQ ID NO: QGIVHLDLKPENIMCVNK ENSG00000065534.14 66 241 SEQ ID NO: TLGDQLSLLLGAR ENSG00000011028.9 66 242 SEQ ID NO: CTHWAEGGK ENSG00000100714.11 65 243 SEQ ID NO: FGLYLPLFKPSVSTSK ENSG00000004864.9 65 244 SEQ ID NO: GSCYPATGDLLVGR ENSG00000172037.9 65 245 SEQ ID NO: VMPLIIQGFK ENSG00000086475.10 65 246 SEQ ID NO: TPLWIGLAGEEGSR ENSG00000011028.9 64 247 SEQ ID NO: TQPDGTSVPGEPASPISQR ENSG00000137497.13 64 248 SEQ ID NO: VWGVPIPVFHHK ENSG00000067704.8 64 249 SEQ ID NO: ALLNVVDNAR ENSG00000105223.14 63 250 SEQ ID NO: GGTTNPHIFPEGSEPK ENSG00000167770.7 63 251 SEQ ID NO: YTVNFLEAK ENSG00000142453.7 63 252 SEQ ID NO: ATIQGVLR ENSG00000196961.8 62 253 SEQ ID NO: GPLGDQYQTVK ENSG00000172037.9 62 254 SEQ ID NO: VAAQVDGGAQVQQVLNIECLR ENSG00000196961.8 62 255 SEQ ID NO: FTPVVCGLR ENSG00000090006.13 61 256 SEQ ID NO: LFPNSLDQTDMHGDSEYNIMFG ENSG00000179218.9 61 257 PDICGPGTK SEQ ID NO: TILLSTTDPADFAVAEALEK ENSG00000130396.16 61 258 SEQ ID NO: LTYLGCASVNAPR ENSG00000011454.12 60 259 SEQ ID NO: SCYLSSLDLLLEHR ENSG00000133315.6 60 260 SEQ ID NO: VVATTQMQAADAR ENSG00000166825.9 60 261 SEQ ID NO: GVGGSQPPDIDKTELVEPTEYLV ENSG00000166825.9 59 262 VHLK SEQ ID NO: KEIHTVPDMGK ENSG00000119383.15 59 263 SEQ ID NO: LFTALFPFEK ENSG00000169896.12 59 264 SEQ ID NO: SLESALK ENSG00000130429.8 59 265 SEQ ID NO: VDDQIAIVFK ENSG00000119383.15 59 266 SEQ ID NO: VLDPAIPIPDPYSSR ENSG00000172037.9 59 267 SEQ ID NO: ATPFIECNGGR ENSG00000134871.13 58 268 SEQ ID NO: CSVCEAPAIAIAVHSQDVSIPHCP ENSG00000134871.13 58 269 AGWR SEQ ID NO: EAQVAHADQQLR ENSG00000137497.13 58 270 SEQ ID NO: EIILDDDECPLQIFR ENSG00000130396.16 58 271 SEQ ID NO: TPAAIPATPVAVSQPIR ENSG00000130396.16 58 272 SEQ ID NO: DLGFFGIYK ENSG00000004864.9 57 273 SEQ ID NO: EERPAPTPWGSK ENSG00000130429.8 57 274 SEQ ID NO: YVGFGNTPPPQK ENSG00000101199.8 57 275 SEQ ID NO: CLFQSPLFAK ENSG00000142453.7 56 276 SEQ ID NO: SETDTSLIR ENSG00000146731.6 56 277 SEQ ID NO: ILETWGELLSK ENSG00000011454.12 54 278 SEQ ID NO: YSGLCPHVVVLVATVR ENSG00000100714.11 54 279 SEQ ID NO: ENSLLFDPLSSSSSNK ENSG00000166825.9 53 280 SEQ ID NO: IKNEAEPEFASR ENSG00000198947.10 53 281 SEQ ID NO: VSAPDGPCPTGFER ENSG00000090006.13 53 282 SEQ ID NO: AQGIAQGAIR ENSG00000172037.9 52 283 SEQ ID NO: KVCGDSDKGFVVINQK ENSG00000146731.6 52 284 SEQ ID NO: LWSGYSLLYFEGQEK ENSG00000134871.13 52 285 SEQ ID NO: VPIWDQDIQFLPGSQK ENSG00000133316.11 52 286 SEQ ID NO: YLSYTLNPDLIR ENSG00000166825.9 52 287 SEQ ID NO: YVIGVGDAFR ENSG00000169896.12 52 288 SEQ ID NO: DLEVVEGSAAR ENSG00000065534.14 51 289 SEQ ID NO: FAVGSGSR ENSG00000130429.8 50 290 SEQ ID NO: GFGQSVVQLQGSR ENSG00000169896.12 50 291 SEQ ID NO: GLPGEVLGAQPGPR ENSG00000134871.13 50 292 SEQ ID NO: LAETLGR ENSG00000169756.12 50 293 SEQ ID NO: LPPKVESLESLYFTPIPAR ENSG00000137497.13 50 294 SEQ ID NO: PTDSKPEDWDKPEHIPDPDAK ENSG00000179218.9 50 295 SEQ ID NO: QLSLPQQEAQK ENSG00000196961.8 50 296 SEQ ID NO: DVTTFFSGK ENSG00000101199.8 49 297 SEQ ID NO: GQVEQANQELQELIQSVK ENSG00000172037.9 49 298 SEQ ID NO: IDDVLHTLTGAMSLLR ENSG00000130396.16 49 299 SEQ ID NO: LQLPNCIEDPVSPIVLR ENSG00000169896.12 49 300 SEQ ID NO: VESLESLYFTPIPAR ENSG00000137497.13 49 301 SEQ ID NO: FGDPLGYEDVIPEADREGVIR ENSG00000169896.12 48 302 SEQ ID NO: LEPNAQAQMYR ENSG00000196961.8 48 303 SEQ ID NO: DSLEDCVTIWGPEGR ENSG00000011028.9 47 304 SEQ ID NO: EAVTEILGIEPDR ENSG00000211460.7 47 305 SEQ ID NO: FQNLDKK ENSG00000130429.8 47 306 SEQ ID NO: GGECASPLPGLR ENSG00000090006.13 47 307 SEQ ID NO: IAVSKPSGPQPQADLQALLQSGA ENSG00000105223.14 47 308 QVR SEQ ID NO: VLELSIPASAEQIQHLAGAIAER ENSG00000172037.9 47 309 SEQ ID NO: AAPVPTAPAAGAPLMDFGNDFV ENSG00000115310.13 46 310 PPAPR SEQ ID NO: GGYTCVCPDGFLLDSSR ENSG00000090006.13 46 311 SEQ ID NO: VLLTRPGEGGTGLPGPPLITR ENSG00000152894.10 46 312 SEQ ID NO: ELQPQQQPR ENSG00000130396.16 45 313 SEQ ID NO: FCQLHSSGARPPAPAVPGLTR ENSG00000090006.13 45 314 SEQ ID NO: LAAGDQLLSVDGR ENSG00000130396.16 45 315 SEQ ID NO: SLTLDTWEPELLK ENSG00000114331.8 45 316 SEQ ID NO: EQVPGFTPR ENSG00000100714.11 44 317 SEQ ID NO: ETGVPIAGR ENSG00000100714.11 44 318 SEQ ID NO: KITIGQAPTEK ENSG00000100714.11 44 319 SEQ ID NO: FSTMPFLYCNPGDVCYYASR ENSG00000134871.13 43 320 SEQ ID NO: LLTIGDANGEIQR ENSG00000142453.7 43 321 SEQ ID NO: LQSQVISELDACK ENSG00000132205.6 43 322 SEQ ID NO: LTILAAR ENSG00000065534.14 43 323 SEQ ID NO: LVECLETVLNK ENSG00000196961.8 43 324 SEQ ID NO: SSPQFGVTLLTYELLQR ENSG00000004864.9 43 325 SEQ ID NO: YQCHEEGLVPSK ENSG00000172037.9 43 326 SEQ ID NO: GCQLCPPFGSEGFR ENSG00000090006.13 42 327 SEQ ID NO: KPGLEEAVESACAMR ENSG00000067704.8 42 328 SEQ ID NO: LVQCVDAFEEK ENSG00000065534.14 42 329 SEQ ID NO: QWFINITDIK ENSG00000067704.8 42 330 SEQ ID NO: SQLEAIFLR ENSG00000105223.14 42 331 SEQ ID NO: VLEGSELELAK ENSG00000137497.13 42 332 SEQ ID NO: VVQDLAAR ENSG00000172037.9 42 333 SEQ ID NO: AIMEFNPR ENSG00000169896.12 41 334 SEQ ID NO: ALAEGGSILSR ENSG00000172037.9 41 335 SEQ ID NO: EICPAGPGYHYSASDLR ENSG00000090006.13 41 336 SEQ ID NO: EQVVEDRPVGGR ENSG00000135052.12 41 337 SEQ ID NO: LYCNPGDVCYYASR ENSG00000134871.13 41 338 SEQ ID NO: TQDASGPELILPASIEFR ENSG00000130396.16 41 339 SEQ ID NO: YSEIEPSTEGEVIYR ENSG00000172037.9 41 340 SEQ ID NO: AWCVNCFACSTCNTK ENSG00000169756.12 40 341 SEQ ID NO: DDPTDSKPEDWDKPEHIPDPDA ENSG00000179218.9 40 342 K SEQ ID NO: IVQATTLLTMDK ENSG00000130396.16 40 343 SEQ ID NO: VDLSTSTDWK ENSG00000133315.6 40 344 SEQ ID NO: AQLLQQTR ENSG00000213380.9 39 345 SEQ ID NO: DVDECQLFR ENSG00000090006.13 39 346 SEQ ID NO: IEGYPDPEVVWFKDDQSIR ENSG00000065534.14 39 347 SEQ ID NO: LSSMAMISGLSGR ENSG00000065534.14 39 348 SEQ ID NO: NNGVLFENQLLQIGVK ENSG00000196961.8 39 349 SEQ ID NO: RADPAELR ENSG00000004864.9 39 350 SEQ ID NO: SAPASQASLR ENSG00000137497.13 39 351 SEQ ID NO: DWEQFEYK ENSG00000137497.13 38 352 SEQ ID NO: IQAELAVILK ENSG00000137497.13 38 353 SEQ ID NO: SNRDELELELAENRK ENSG00000137497.13 38 354 SEQ ID NO: TPVPEKVPPPKPATPDFR ENSG00000065534.14 38 355 SEQ ID NO: VSLEPHQGPGTPESK ENSG00000137497.13 38 356 SEQ ID NO: CTEPEDQLYYVK ENSG00000106066.9 37 357 SEQ ID NO: ECYFDTAAPDACDNILAR ENSG00000090006.13 37 358 SEQ ID NO: FGLGSVAGAVGATAVYPIDLVK ENSG00000004864.9 37 359 SEQ ID NO: GQEDAILSYEPVTR ENSG00000082458.7 37 360 SEQ ID NO: IMELEGR ENSG00000135052.12 37 361 SEQ ID NO: TCVSLAVSR ENSG00000196961.8 37 362 SEQ ID NO: TILTLTGVSTLGDVK ENSG00000184207.8 37 363 SEQ ID NO: VLQIVTNRDDVQGYAAK ENSG00000196961.8 37 364 SEQ ID NO: AFGFSHLEALLDDSKELQR ENSG00000167770.7 36 365 SEQ ID NO: AGPDSAGIALYSHEDVCVFK ENSG00000142453.7 36 366 SEQ ID NO: AQGVLAAQAR ENSG00000172037.9 36 367 SEQ ID NO: LPSFQQSCR ENSG00000213380.9 36 368 SEQ ID NO: MLSSFLSEDVFK ENSG00000166825.9 36 369 SEQ ID NO: DTEQTLYQVQER ENSG00000172037.9 35 370 SEQ ID NO: DVEVTKEEFVLAAQK ENSG00000004864.9 35 371 SEQ ID NO: INQLSEENGDLSFK ENSG00000137497.13 35 372 SEQ ID NO: LNIPATNVFANR ENSG00000146733.9 35 373 SEQ ID NO: SLVKPITQLLGR ENSG00000169896.12 35 374 SEQ ID NO: YLCEGTESPYQTGQLHPAIR ENSG00000152894.10 35 375 SEQ ID NO: ASMQPIQIAEGTGITTR ENSG00000137497.13 34 376 SEQ ID NO: IAGALGGLLTPLFLR ENSG00000064545.10 34 377 SEQ ID NO: LGASALDSIQEFR ENSG00000032444.11 34 378 SEQ ID NO: SGTIFDNFLITNDEAYAEEFGNET ENSG00000179218.9 34 379 WGVTK SEQ ID NO: TVLDLQSSLAGVSENLK ENSG00000132205.6 34 380 SEQ ID NO: AGPDLASCLDVDECRER ENSG00000090006.13 33 381 SEQ ID NO: EGGTAAGAGLDSLHK ENSG00000130429.8 33 382 SEQ ID NO: FYEFSQR ENSG00000153310.14 33 383 SEQ ID NO: GEWIKPGAIVIDCGINYVPDDK ENSG00000100714.11 33 384 SEQ ID NO: NDPYHPDHFNCANCGK ENSG00000169756.12 33 385 SEQ ID NO: SLEPHQGPGTPESK ENSG00000137497.13 33 386 SEQ ID NO: SLGEENFEVVK ENSG00000132561.9 33 387 SEQ ID NO: THIDTVINALK ENSG00000196961.8 33 388 SEQ ID NO: VHAELADVLTEAVVDSILAIKK ENSG00000146731.6 33 389 SEQ ID NO: VMQHQYQVSNLGQR ENSG00000169896.12 33 390 SEQ ID NO: ASFITPVPGGVGPMTVAMLMQ ENSG00000100714.11 32 391 STVESAK SEQ ID NO: FEHFIEGGR ENSG00000167770.7 32 392 SEQ ID NO: LQQAQLYPIAIFIKPK ENSG00000082458.7 32 393 SEQ ID NO: MTLADIER ENSG00000004864.9 32 394 SEQ ID NO: TVELLSGVVDQTK ENSG00000004864.9 32 395 SEQ ID NO: AMDYDLLLR ENSG00000172037.9 31 396 SEQ ID NO: DFGSFDK ENSG00000112096.12 31 397 SEQ ID NO: EPAVYFKEQFLDGDGWTSR ENSG00000179218.9 31 398 SEQ ID NO: FLINLEGGDIREESSYK ENSG00000067704.8 31 399 SEQ ID NO: GEWIKPGAIVIDCGINYVPDDKK ENSG00000100714.11 31 400 PNGR SEQ ID NO: HAVVVGR ENSG00000100714.11 31 401 SEQ ID NO: LEGDTFLLLIQSLK ENSG00000104450.8 31 402 SEQ ID NO: NTSVVDSEPVR ENSG00000162614.14 31 403 SEQ ID NO: PGTTDQVPR ENSG00000113657.8 31 404 SEQ ID NO: QLDQHLDLLK ENSG00000172037.9 31 405 SEQ ID NO: TVIVHGFTLGEK ENSG00000067704.8 31 406 SEQ ID NO: YAPDDIPNINSTCFK ENSG00000130396.16 31 407 SEQ ID NO: AADLLYAMCDR ENSG00000196961.8 30 408 SEQ ID NO: EMGEAFAADIPR ENSG00000196961.8 30 409 SEQ ID NO: IQGTLQPHAR ENSG00000172037.9 30 410 SEQ ID NO: LPIAVNGSLIYGVCAGK ENSG00000059691.7 30 411 SEQ ID NO: VNDDLISEFPHK ENSG00000082458.7 30 412 SEQ ID NO: DGGCSLPILR ENSG00000090006.13 29 413 SEQ ID NO: ENVDYIIQELR ENSG00000136631.8 29 414 SEQ ID NO: GAAVDEYFR ENSG00000142453.7 29 415 SEQ ID NO: GETAVPGAPEALR ENSG00000184207.8 29 416 SEQ ID NO: ILYSFATAFR ENSG00000011454.12 29 417 SEQ ID NO: NVFECNDQVVK ENSG00000169896.12 29 418 SEQ ID NO: STGSFVGELMYK ENSG00000004864.9 29 419 SEQ ID NO: TIRDLEVVEGSAAR ENSG00000065534.14 29 420 SEQ ID NO: TVFEALQAPACHENMVK ENSG00000196961.8 29 421 SEQ ID NO: VGLLQYGSTVK ENSG00000132561.9 29 422 SEQ ID NO: YVLSNQYRPDISPTER ENSG00000130396.16 29 423 SEQ ID NO: AEAELEYNPEHVSR ENSG00000067704.8 28 424 SEQ ID NO: ASPDLVPMGEWTAR ENSG00000196961.8 28 425 SEQ ID NO: CEACAPGHFGDPSRPGGR ENSG00000172037.9 28 426 SEQ ID NO: EDGYSDASGFGYCFR ENSG00000090006.13 28 427 SEQ ID NO: GDLIGVVEALTR ENSG00000032444.11 28 428 SEQ ID NO: LAILQVGNRDDSNLYINVK ENSG00000100714.11 28 429 SEQ ID NO: NDAGQAECSCQVTVDDAPASE ENSG00000065534.14 28 430 NTK SEQ ID NO: QNWFEAFEILDK ENSG00000106066.9 28 431 SEQ ID NO: SSEGLLATATVPLDLFK ENSG00000157617.12 28 432 SEQ ID NO: STTTIGLVQALGAHLYQNVFACV ENSG00000100714.11 28 433 R SEQ ID NO: VLVLEMFSGGDAAALER ENSG00000172037.9 28 434 SEQ ID NO: KQVAPEKPVK ENSG00000113387.7 27 435 SEQ ID NO: LQELEGTYEENER ENSG00000172037.9 27 436 SEQ ID NO: LVEQHGSDIWWTLPPEQLLPK ENSG00000067704.8 27 437 SEQ ID NO: NPTFMCLALHCIANVGSR ENSG00000196961.8 27 438 SEQ ID NO: SSDGRPDSGGTLR ENSG00000130396.16 27 439 SEQ ID NO: AAPQPLNLVSSVTLSK ENSG00000114861.14 26 440 SEQ ID NO: AVQAQGGESQQEAQR ENSG00000137497.13 26 441 SEQ ID NO: DFLNQEGADPDSIEMVATR ENSG00000172037.9 26 442 SEQ ID NO: GQVLDVVER ENSG00000172037.9 26 443 SEQ ID NO: LALIQPSR ENSG00000146733.9 26 444 SEQ ID NO: LQQDVLQFQK ENSG00000135052.12 26 445 SEQ ID NO: LTFEELER ENSG00000162614.14 26 446 SEQ ID NO: QVTPLFIHFR ENSG00000166825.9 26 447 SEQ ID NO: SFNVQDLLPDHEYK ENSG00000065534.14 26 448 SEQ ID NO: SSCISQHVISEAK ENSG00000090006.13 26 449 SEQ ID NO: VLQIVTNR ENSG00000196961.8 26 450 SEQ ID NO: VVGDVAYDEAK ENSG00000100714.11 26 451 SEQ ID NO: ALQSGPPQSR ENSG00000136231.9 25 452 SEQ ID NO: ITIGQAPTEK ENSG00000100714.11 25 453 SEQ ID NO: KAQGVLAAQAR ENSG00000172037.9 25 454 SEQ ID NO: LKENLYPYLGPSTLR ENSG00000136631.8 25 455 SEQ ID NO: LPVTINK ENSG00000196961.8 25 456 SEQ ID NO: SILTAIPNDDPYFHITK ENSG00000213380.9 25 457 SEQ ID NO: SLGNVIHPDVVVNGGQDQSK ENSG00000067704.8 25 458 SEQ ID NO: AVQTSIATAYR ENSG00000114331.8 24 459 SEQ ID NO: DASKPEDWDER ENSG00000179218.9 24 460 SEQ ID NO: IPVSGPFLVK ENSG00000136231.9 24 461 SEQ ID NO: LLGPAGLTWER ENSG00000138162.13 24 462 SEQ ID NO: LPVEAFSAVFTK ENSG00000032444.11 24 463 SEQ ID NO: SEESTTVHSSPGATGTALFPTR ENSG00000205277.5 24 464 SEQ ID NO: SEESTTVHSSPGATGTALFPTR ENSG00000205277.5 24 465 SEQ ID NO: SEESTTVHSSPGATGTALFPTR ENSG00000205277.5 24 466 SEQ ID NO: TKVHAELADVLTEAVVDSILAIK ENSG00000146731.6 24 467 SEQ ID NO: YGEGHQAWIIGIVEK ENSG00000086475.10 24 468 SEQ ID NO: ADLYLEGK ENSG00000067704.8 23 469 SEQ ID NO: CLEEKNEILQGK ENSG00000137497.13 23 470 SEQ ID NO: FIFDCVSQEYGINPER ENSG00000184207.8 23 471 SEQ ID NO: IHGTEEGQQILK ENSG00000137497.13 23 472 SEQ ID NO: KIQTQLQR ENSG00000166825.9 23 473 SEQ ID NO: KVVGDVAYDEAK ENSG00000100714.11 23 474 SEQ ID NO: LDSISGNLQR ENSG00000132205.6 23 475 SEQ ID NO: LFEDLEFQQLER ENSG00000019144.12 23 476 SEQ ID NO: SLGNVIHPDVVVNGGQDQSKEP ENSG00000067704.8 23 477 PYGADVLR SEQ ID NO: TEVNSGFFYK ENSG00000146731.6 23 478 SEQ ID NO: TSAGTFPGSQPQAPASPVLPARP ENSG00000090006.13 23 479 PPPPLPR SEQ ID NO: VHSPQQVDFR ENSG00000065534.14 23 480 SEQ ID NO: VLTGNTIALVLGGGGAR ENSG00000032444.11 23 481 SEQ ID NO: VSALSVVR ENSG00000004864.9 23 482 SEQ ID NO: ASLENGVLLCDLINK ENSG00000136153.15 22 483 SEQ ID NO: ETLIDVAR ENSG00000146731.6 22 484 SEQ ID NO: FESKPQSQEVK ENSG00000065534.14 22 485 SEQ ID NO: GHLQIAACPNQDPLQGTTGLIPL ENSG00000112096.12 22 486 LGIDVWEHAYYLQYK SEQ ID NO: GICEALEDSDGRQDSPAGELPK ENSG00000132561.9 22 487 SEQ ID NO: GYLAPSGDLSLR ENSG00000090006.13 22 488 SEQ ID NO: LQSQLLSIEKEVEEYK ENSG00000106976.14 22 489 SEQ ID NO: SGQGSDRGSGSRPGIEGDTPR ENSG00000113657.8 22 490 SEQ ID NO: VAISTFQK ENSG00000213380.9 22 491 SEQ ID NO: GQDIFIIQTIPR ENSG00000161542.12 21 492 SEQ ID NO: ITLDAQDVLAHLVQMAFK ENSG00000130396.16 21 493 SEQ ID NO: RTEVPPLLLILDR ENSG00000136631.8 21 494 SEQ ID NO: SSPPVQFSLLHSK ENSG00000196961.8 21 495 SEQ ID NO: SSTGSPTSPLNAEK ENSG00000065534.14 21 496 SEQ ID NO: TKFPAEQYYR ENSG00000211460.7 21 497 SEQ ID NO: ANFWYQPSFHGVDLSALR ENSG00000142453.7 20 498 SEQ ID NO: DAQIAMMQQR ENSG00000137497.13 20 499 SEQ ID NO: EHGAFDAVK ENSG00000100714.11 20 500 SEQ ID NO: GLAQADGTLITCVDSGILR ENSG00000133316.11 20 501 SEQ ID NO: GLNCEQCQDFYR ENSG00000172037.9 20 502 SEQ ID NO: KVVATTQMQAADAR ENSG00000166825.9 20 503 SEQ ID NO: MKLTHSLQEELEK ENSG00000151914.13 20 504 SEQ ID NO: NIDVFNVEDQKR ENSG00000135052.12 20 505 SEQ ID NO: QASDKDDRPFQGEDVENSR ENSG00000130396.16 20 506 SEQ ID NO: SLDQTDMHGDSEYNIMFGPDIC ENSG00000179218.9 20 507 GPGTK SEQ ID NO: STIFHSSPDASGTTPSSAHSTTSG ENSG00000205277.5 20 508 R SEQ ID NO: STIFHSSPDASGTTPSSAHSTTSG ENSG00000205277.5 20 509 R SEQ ID NO: STIFHSSPDASGTTPSSAHSTTSG ENSG00000205277.5 20 510 R SEQ ID NO: STIFHSSPDASGTTPSSAHSTTSG ENSG00000205277.5 20 511 R SEQ ID NO: VCLHVQK ENSG00000169896.12 20 512 SEQ ID NO: VSQFLQVLETDLYR ENSG00000213380.9 20 513 SEQ ID NO: VSSTATTQDVIETLAEK ENSG00000130396.16 20 514 SEQ ID NO: YNTRPLGQEPPR ENSG00000090006.13 20 515 SEQ ID NO: ANHPMDAEVTK ENSG00000196961.8 19 516 SEQ ID NO: ASELGHSLNENVLKPAQEK ENSG00000101199.8 19 517 SEQ ID NO: AWVSHDSTVCLADADKK ENSG00000130429.8 19 518 SEQ ID NO: FSYDLSQCINQMK ENSG00000135052.12 19 519 SEQ ID NO: IYQFTAASPK ENSG00000005020.8 19 520 SEQ ID NO: KQDEPIDLFMIEIMEMK ENSG00000146731.6 19 521 SEQ ID NO: NIMAGLQQTNSEK ENSG00000198947.10 19 522 SEQ ID NO: RPDYLK ENSG00000112096.12 19 523 SEQ ID NO: SEESTTVHSSPVATATTPSPAR ENSG00000205277.5 19 524 SEQ ID NO: SEESTTVHSSPVATATTPSPAR ENSG00000205277.5 19 525 SEQ ID NO: SEESTTVHSSPVATATTPSPAR ENSG00000205277.5 19 526 SEQ ID NO: SEESTTVHSSPVATATTPSPAR ENSG00000205277.5 19 527 SEQ ID NO: THLTSLK ENSG00000211460.7 19 528 SEQ ID NO: AQEAEQLLR ENSG00000172037.9 18 529 SEQ ID NO: AQIINDAFNLASAHK ENSG00000166825.9 18 530 SEQ ID NO: DQLGGWFQSSLLTSVAAR ENSG00000067704.8 18 531 SEQ ID NO: GADDIELLPEAQHK ENSG00000100714.11 18 532 SEQ ID NO: GFSHLEALLDDSK ENSG00000167770.7 18 533 SEQ ID NO: GLLTDSPAATVLAEAR ENSG00000019144.12 18 534 SEQ ID NO: HSNFLGAYDSIR ENSG00000172037.9 18 535 SEQ ID NO: KNEFQGELEK ENSG00000135052.12 18 536 SEQ ID NO: SFLEEVLASGLHSR ENSG00000136631.8 18 537 SEQ ID NO: TEILGIEPDREK ENSG00000211460.7 18 538 SEQ ID NO: VILLDPSIIEAK ENSG00000104450.8 18 539 SEQ ID NO: AETVQAALEEAQR ENSG00000172037.9 17 540 SEQ ID NO: AFVENYPQFK ENSG00000136631.8 17 541 SEQ ID NO: DFISNLLK ENSG00000065534.14 17 542 SEQ ID NO: DGFFGLSISDR ENSG00000172037.9 17 543 SEQ ID NO: DHVFQVNNFEALK ENSG00000169896.12 17 544 SEQ ID NO: DPTDSKPEDWDKPEHIPDPDAK ENSG00000179218.9 17 545 SEQ ID NO: KIIELK ENSG00000146731.6 17 546 SEQ ID NO: LCCPVALAQDVTGALEDALAK ENSG00000213380.9 17 547 SEQ ID NO: PAIAHLIHSLNPVR ENSG00000106066.9 17 548 SEQ ID NO: PSSTPTTHFSASSTTLGR ENSG00000205277.5 17 549 SEQ ID NO: PSSTPTTHFSASSTTLGR ENSG00000205277.5 17 550 SEQ ID NO: PSSTPTTHFSASSTTLGR ENSG00000205277.5 17 551 SEQ ID NO: PSSTPTTHFSASSTTLGR ENSG00000205277.5 17 552 SEQ ID NO: PSSTPTTHFSASSTTLGR ENSG00000205277.5 17 553 SEQ ID NO: PSSTPTTHFSASSTTLGR ENSG00000205277.5 17 554 SEQ ID NO: PSSTPTTHFSASSTTLGR ENSG00000205277.5 17 555 SEQ ID NO: QFVTGIIDSLTISPK ENSG00000132561.9 17 556 SEQ ID NO: SEAVLQSPEFAIFR ENSG00000198947.10 17 557 SEQ ID NO: TTQGLTALLLSLK ENSG00000136631.8 17 558 SEQ ID NO: VPLSVQLKPEVSPTQDIR ENSG00000125826.15 17 559 SEQ ID NO: VTAIDFR ENSG00000004864.9 17 560 SEQ ID NO: YLIFPNPVCLEPGISYK ENSG00000172037.9 17 561 SEQ ID NO: YRLPNTLKPDSYR ENSG00000166825.9 17 562 SEQ ID NO: AFLLSLAALR ENSG00000105223.14 16 563 SEQ ID NO: DLAQYSSNDAVVETSLTK ENSG00000114331.8 16 564 SEQ ID NO: DRLPQEPGREQVVEDRPVGGR ENSG00000135052.12 16 565 SEQ ID NO: EAIQHPADEKLQEK ENSG00000153310.14 16 566 SEQ ID NO: EFQNNPNPR ENSG00000169896.12 16 567 SEQ ID NO: ELSAALQDKK ENSG00000137497.13 16 568 SEQ ID NO: ELSGSGLER ENSG00000213380.9 16 569 SEQ ID NO: ELWILNR ENSG00000166825.9 16 570 SEQ ID NO: FSTEYELQQLEQFKK ENSG00000166825.9 16 571 SEQ ID NO: GPALCGSQR ENSG00000090006.13 16 572 SEQ ID NO: GPLEPGPPKPGVPQEPGR ENSG00000125826.15 16 573 SEQ ID NO: GSLYQCDYSTGSCEPIR ENSG00000169896.12 16 574 SEQ ID NO: IQTQLQR ENSG00000166825.9 16 575 SEQ ID NO: KNSSIIGDYKQICSQLSER ENSG00000011454.12 16 576 SEQ ID NO: LEINFEELLK ENSG00000162614.14 16 577 SEQ ID NO: LIVPEPDVDFDAK ENSG00000132205.6 16 578 SEQ ID NO: LVGPEGFVVTEAGFGADIGMEK ENSG00000100714.11 16 579 SEQ ID NO: QEHCGCYTLLVENK ENSG00000065534.14 16 580 SEQ ID NO: RSQAGVSSGAPPGR ENSG00000137497.13 16 581 SEQ ID NO: SPGSTPTTHFPASSTTSGHSEK ENSG00000205277.5 16 582 SEQ ID NO: SPGSTPTTHFPASSTTSGHSEK ENSG00000205277.5 16 583 SEQ ID NO: SPGSTPTTHFPASSTTSGHSEK ENSG00000205277.5 16 584 SEQ ID NO: SPGSTPTTHFPASSTTSGHSEK ENSG00000205277.5 16 585 SEQ ID NO: VLSQIDVAQK ENSG00000198947.10 16 586 SEQ ID NO: YGGMFCNVEGAFESK ENSG00000113657.8 16 587 SEQ ID NO: ATVVVEATEPEPSGSIANPAASTS ENSG00000131711.10 15 588 PSLSHR SEQ ID NO: EMTADVIELK ENSG00000067704.8 15 589 SEQ ID NO: GEQGFMGNTGPTGAVGDRGPK ENSG00000134871.13 15 590 SEQ ID NO: LAEAELEYNPEHVSR ENSG00000067704.8 15 591 SEQ ID NO: LESEEDVSQAFLEAVAEEKPHVK ENSG00000065534.14 15 592 PYFSK SEQ ID NO: LMCELGNDVINR ENSG00000114331.8 15 593 SEQ ID NO: QQQDYWLIDVR ENSG00000166825.9 15 594 SEQ ID NO: SSEGGTAAGAGLDSLHK ENSG00000130429.8 15 595 SEQ ID NO: SYKPVFWSPSSR ENSG00000067704.8 15 596 SEQ ID NO: TAHLDEEVNKGDILVVATGQPE ENSG00000100714.11 15 597 MVK SEQ ID NO: TRPDGNCFYR ENSG00000167770.7 15 598 SEQ ID NO: TSGQCLCR ENSG00000172037.9 15 599 SEQ ID NO: AFCVANK ENSG00000114331.8 14 600 SEQ ID NO: AMISGLSGR ENSG00000065534.14 14 601 SEQ ID NO: AVESSKPLSNAQPSGPLKPVGN ENSG00000065534.14 14 602 SEQ ID NO: AYHSFLVEPISCHAWNKDR ENSG00000130429.8 14 603 SEQ ID NO: EGVVDIYNCVK ENSG00000152894.10 14 604 SEQ ID NO: GTWIHPEIDNPEYSPDPSIYAYD ENSG00000179218.9 14 605 NFGVLGLDLWQVK SEQ ID NO: HLTQAVCTVK ENSG00000141447.12 14 606 SEQ ID NO: ITISPLQELTLYNPER ENSG00000136231.9 14 607 SEQ ID NO: LACESASSTEVSGALK ENSG00000169896.12 14 608 SEQ ID NO: LDCTQCLQHPWLMK ENSG00000065534.14 14 609 SEQ ID NO: LDEEAENLVATVVPTHLAAAVPE ENSG00000119383.15 14 610 VAVYLK SEQ ID NO: LPEDDEPPARPPPPPPASVSPQA ENSG00000115310.13 14 611 EPVWTPPAPAPAAPPSTPAAPK SEQ ID NO: LPNTLKPDSYR ENSG00000166825.9 14 612 SEQ ID NO: LSSTQQSLAEK ENSG00000082805.15 14 613 SEQ ID NO: LVALETGIQK ENSG00000019144.12 14 614 SEQ ID NO: MHGGGPTVTAGLPLPK ENSG00000100714.11 14 615 SEQ ID NO: QQALELVVQEVSSVLR ENSG00000157617.12 14 616 SEQ ID NO: QSMAFSILNTPK ENSG00000137497.13 14 617 SEQ ID NO: SSNLLDLK ENSG00000142453.7 14 618 SEQ ID NO: VLQDQLK ENSG00000135052.12 14 619 SEQ ID NO: WVSHDSTVCLADADKK ENSG00000130429.8 14 620 SEQ ID NO: AAQLDGLEAR ENSG00000172037.9 13 621 SEQ ID NO: ANALASATCER ENSG00000169756.12 13 622 SEQ ID NO: ATDNEPSQFSEPR ENSG00000132205.6 13 623 SEQ ID NO: CGFSELYSWQR ENSG00000067704.8 13 624 SEQ ID NO: DLLQAAQDK ENSG00000172037.9 13 625 SEQ ID NO: EPAPASPAPAGVEIR ENSG00000113657.8 13 626 SEQ ID NO: EYELFEFR ENSG00000136631.8 13 627 SEQ ID NO: HKPGIVQETTFDLGGDIHSGTAL ENSG00000130396.16 13 628 PTSK SEQ ID NO: IWDLQGSEEPVFR ENSG00000133316.11 13 629 SEQ ID NO: LFGDVEASLGR ENSG00000213380.9 13 630 SEQ ID NO: LHTLGDNLLDPR ENSG00000172037.9 13 631 SEQ ID NO: RFSDIQIR ENSG00000100714.11 13 632 SEQ ID NO: SEVYGPMK ENSG00000166825.9 13 633 SEQ ID NO: SLSESAATR ENSG00000159788.14 13 634 SEQ ID NO: VTCVEMEPLAEYVVR ENSG00000152894.10 13 635 SEQ ID NO: YLFEEDNLLR ENSG00000132561.9 13 636 SEQ ID NO: AAECLDVDECHR ENSG00000090006.13 12 637 SEQ ID NO: AGMSSLKG ENSG00000146731.6 12 638 SEQ ID NO: ALASATCER ENSG00000169756.12 12 639 SEQ ID NO: CDSHDDPALGLVSGQCR ENSG00000172037.9 12 640 SEQ ID NO: DCSIALPYVCK ENSG00000011028.9 12 641 SEQ ID NO: DISLQGPGLAPEHCYIENLR ENSG00000019144.12 12 642 SEQ ID NO: FVLDHEDGLNLNEDLENFLQK ENSG00000137497.13 12 643 SEQ ID NO: GANQHATDEEGKDPLSIAVEAA ENSG00000114331.8 12 644 NADIVTLLR SEQ ID NO: GFSHLEALLDDSKELQR ENSG00000167770.7 12 645 SEQ ID NO: GSGVSNFAQLIVR ENSG00000152894.10 12 646 SEQ ID NO: IINDAFNLASAHK ENSG00000166825.9 12 647 SEQ ID NO: KVVQSLEQTAR ENSG00000211460.7 12 648 SEQ ID NO: QPAVEEPAEVTATVLASR ENSG00000076662.5 12 649 SEQ ID NO: QTQVLGLTQTCETLK ENSG00000169896.12 12 650 SEQ ID NO: RVEDAYILTCNVSLEYEK ENSG00000146731.6 12 651 SEQ ID NO: TLDFDALSVGQR ENSG00000113657.8 12 652 SEQ ID NO: VVNAMGK ENSG00000169756.12 12 653 SEQ ID NO: AKIDDPTDSKPEDWDKPEHIPD ENSG00000179218.9 11 654 SEQ ID NO: ALEQLLTELDDFLK ENSG00000169129.10 11 655 SEQ ID NO: ASKPEDWDER ENSG00000179218.9 11 656 SEQ ID NO: DLNQLFQQDSSSR ENSG00000082805.15 11 657 SEQ ID NO: ETPGRPPDPTGAPLPGPTGDPVK ENSG00000032444.11 11 658 PTSLETPSAPLLSR SEQ ID NO: GSACEEDVDECAQEPPPCGPGR ENSG00000090006.13 11 659 SEQ ID NO: KASSEGGTAAGAGLDSLHK ENSG00000130429.8 11 660 SEQ ID NO: LGFITNNSSK ENSG00000184207.8 11 661 SEQ ID NO: LPSHSDFLAELR ENSG00000169896.12 11 662 SEQ ID NO: LQDVHVAEGK ENSG00000065534.14 11 663 SEQ ID NO: LVTCTGYHQVR ENSG00000133316.11 11 664 SEQ ID NO: SIQLPTTVR ENSG00000166825.9 11 665 SEQ ID NO: VLSELGR ENSG00000067704.8 11 666 SEQ ID NO: WAPNENKFAVGSGSR ENSG00000130429.8 11 667 SEQ ID NO: AQELQQTGVLGAFESSFWHMQ ENSG00000172037.9 10 668 EK SEQ ID NO: ASAAAAAGGGATGHPGGGQGA ENSG00000104450.8 10 669 ENPAGLK SEQ ID NO: EAENFHEEDDVDVRPAR ENSG00000162614.14 10 670 SEQ ID NO: ERLPSHSDFLAELR ENSG00000169896.12 10 671 SEQ ID NO: EWSLESSPAQNWTPPQPR ENSG00000101199.8 10 672 SEQ ID NO: FYALSASFEPFSNKG ENSG00000179218.9 10 673 SEQ ID NO: GISLNPEQWSQLKEQISDIDDAV ENSG00000113387.7 10 674 R SEQ ID NO: HPLLVGHMPVMVAK ENSG00000104728.11 10 675 SEQ ID NO: IAHGNSSIIADR ENSG00000100714.11 10 676 SEQ ID NO: IYADSLKPNIPYK ENSG00000130396.16 10 677 SEQ ID NO: LAILDSQAGQIR ENSG00000019144.12 10 678 SEQ ID NO: NMVVDDDSPEMYK ENSG00000162614.14 10 679 SEQ ID NO: NRLDCTQCLQHPWLMK ENSG00000065534.14 10 680 SEQ ID NO: PVLLQVAESAYR ENSG00000004864.9 10 681 SEQ ID NO: QEPLGSDSEGVNCLAYDEAIMA ENSG00000167770.7 10 682 QQDR SEQ ID NO: QEVEELWIGLNDLK ENSG00000011028.9 10 683 SEQ ID NO: SFVIHNLPVLAK ENSG00000086475.10 10 684 SEQ ID NO: STTFHSSPR ENSG00000205277.5 10 685 SEQ ID NO: STTFHSSPR ENSG00000205277.5 10 686 SEQ ID NO: STTFHSSPR ENSG00000205277.5 10 687 SEQ ID NO: TAAGLMHTFNAHAATDITGFGIL ENSG00000086475.10 10 688 GHAQNLAK SEQ ID NO: TGAFGLR ENSG00000172037.9 10 689 SEQ ID NO: TSLTVVLLR ENSG00000076662.5 10 690 SEQ ID NO: VPPLLIYGPFGTGK ENSG00000130589.12 10 691 SEQ ID NO: VPSFAAGR ENSG00000136231.9 10 692 SEQ ID NO: VPVGDQPPDIEFQIR ENSG00000106976.14 10 693 SEQ ID NO: VYDPASPQR ENSG00000133316.11 10 694 SEQ ID NO: WFYIDFGGVKPMGSEPVPK ENSG00000004864.9 10 695 SEQ ID NO: WTPPAPAPAAPPSTPAAPK ENSG00000115310.13 10 696 SEQ ID NO: YDNQWFHGCTSTGR ENSG00000011028.9 10 697 SEQ ID NO: YFSYDCGADFPGVPLAPPR ENSG00000172037.9 10 698 SEQ ID NO: YGDEEKDKGLQTSQDAR ENSG00000179218.9 10 699 SEQ ID NO: YLETADYAIR ENSG00000196961.8 10 700 SEQ ID NO: AKQPDLAPGLTTIGASPTQTVTL ENSG00000198947.10 9 701 VTQPVVTK SEQ ID NO: ASPLLPANHVTMAK ENSG00000067704.8 9 702 SEQ ID NO: AVLELLQRPGNAR ENSG00000105963.9 9 703 SEQ ID NO: CFQVQGQEPQSR ENSG00000011028.9 9 704 SEQ ID NO: DKGLQTSQDAR ENSG00000179218.9 9 705 SEQ ID NO: DLTALSNMLPK ENSG00000166825.9 9 706 SEQ ID NO: DPFSLDALSK ENSG00000146731.6 9 707 SEQ ID NO: FGDPLGYEDVIPEADR ENSG00000169896.12 9 708 SEQ ID NO: FGLYLPLFK ENSG00000004864.9 9 709 SEQ ID NO: FSTEYELQQLEQFK ENSG00000166825.9 9 710 SEQ ID NO: GAVYLFHGTSGSGISPSHSQR ENSG00000169896.12 9 711 SEQ ID NO: HLCELLAQQF ENSG00000196961.8 9 712 SEQ ID NO: ILDQENLSSTALVK ENSG00000169129.10 9 713 SEQ ID NO: ISETTMLQSGMK ENSG00000130396.16 9 714 SEQ ID NO: ISYHGSCPQGLADSAWIPFR ENSG00000011028.9 9 715 SEQ ID NO: KQNWFEAFEILDK ENSG00000106066.9 9 716 SEQ ID NO: PISLVFLVPVR ENSG00000169896.12 9 717 SEQ ID NO: SKESSQVTSR ENSG00000136631.8 9 718 SEQ ID NO: SPPPCTYGR ENSG00000090006.13 9 719 SEQ ID NO: SQLNCLLLSGR ENSG00000133316.11 9 720 SEQ ID NO: TPLSAAAHTHPVYCVNVVGTQN ENSG00000158560.10 9 721 AHNLITVSTDGK SEQ ID NO: VNYDEENWR ENSG00000166825.9 9 722 SEQ ID NO: VSFVIHNLPVLAK ENSG00000086475.10 9 723 SEQ ID NO: VTLRPYLTPNDR ENSG00000166825.9 9 724 SEQ ID NO: WNVINWENVTER ENSG00000112096.12 9 725 SEQ ID NO: ADTDGGLIFR ENSG00000163975.7 8 726 SEQ ID NO: AGYTGLR ENSG00000172037.9 8 727 SEQ ID NO: AVESSKPLSNAQPSGPLKPVGNA ENSG00000065534.14 8 728 K SEQ ID NO: CSEGFVLAEDGRR ENSG00000132561.9 8 729 SEQ ID NO: DLMVLNDVYR ENSG00000166825.9 8 730 SEQ ID NO: FPAEQYYR ENSG00000211460.7 8 731 SEQ ID NO: FTGHCSCRPGVSGVR ENSG00000172037.9 8 732 SEQ ID NO: GDPGDTGAPGPVGMK ENSG00000134871.13 8 733 SEQ ID NO: GGPSLSSVLNELPSAATLR ENSG00000167608.7 8 734 SEQ ID NO: IKDPDASKPEDWDERAK ENSG00000179218.9 8 735 SEQ ID NO: ILCIGAVPGLQPR ENSG00000110237.3 8 736 SEQ ID NO: IQSDLTSHEISLEEMKK ENSG00000198947.10 8 737 SEQ ID NO: ITGHFYACQVAQR ENSG00000136231.9 8 738 SEQ ID NO: KVVGDVAYDEAKER ENSG00000100714.11 8 739 SEQ ID NO: LDTDILLGATCGLK ENSG00000184207.8 8 740 SEQ ID NO: LVSAVVEYGGK ENSG00000136631.8 8 741 SEQ ID NO: MLGVAAGMTHSNMANALASAT ENSG00000169756.12 8 742 CER SEQ ID NO: NIPNGLQEFLDPLCQR ENSG00000130396.16 8 743 SEQ ID NO: QADIIGKPSR ENSG00000184207.8 8 744 SEQ ID NO: QEISIMNCLHHPK ENSG00000065534.14 8 745 SEQ ID NO: QIVSEMLR ENSG00000196961.8 8 746 SEQ ID NO: RAEQLLQDAR ENSG00000172037.9 8 747 SEQ ID NO: RFENAPDSAK ENSG00000082805.15 8 748 SEQ ID NO: SGAPWFK ENSG00000162614.14 8 749 SEQ ID NO: SIVEHVASK ENSG00000146733.9 8 750 SEQ ID NO: SLVGLSQER ENSG00000130396.16 8 751 SEQ ID NO: TVNELQNLSSAEVVVPR ENSG00000136231.9 8 752 SEQ ID NO: VIAVVNK ENSG00000130396.16 8 753 SEQ ID NO: VSHSELR ENSG00000146733.9 8 754 SEQ ID NO: WSDGVGFSYHNFDR ENSG00000011028.9 8 755 SEQ ID NO: YGADDIELLPEAQHK ENSG00000100714.11 8 756 SEQ ID NO: AKPEASFQVWNK ENSG00000073849.10 7 757 SEQ ID NO: ALQLSNSPGASSAFLK ENSG00000170776.15 7 758 SEQ ID NO: ASSEGGTAAGAGLDSLHKNSVS ENSG00000130429.8 7 759 QISVLSGGK SEQ ID NO: AVEMAAQR ENSG00000184207.8 7 760 SEQ ID NO: AVLELLQR ENSG00000105963.9 7 761 SEQ ID NO: AYAQQLADWAR ENSG00000165912.11 7 762 SEQ ID NO: DHSAIPVINR ENSG00000166825.9 7 763 SEQ ID NO: DLRDPAVCR ENSG00000172037.9 7 764 SEQ ID NO: FGSCVPHTTRPR ENSG00000082458.7 7 765 SEQ ID NO: GPQYGTLEK ENSG00000165912.11 7 766 SEQ ID NO: HWDDVVCESR ENSG00000172037.9 7 767 SEQ ID NO: IVLYQTDASLTPWTVR ENSG00000032444.11 7 768 SEQ ID NO: KVHSPQQVDFR ENSG00000065534.14 7 769 SEQ ID NO: LCTDHGSQLVTITNR ENSG00000011028.9 7 770 SEQ ID NO: LDFLPDMMVEGR ENSG00000048740.13 7 771 SEQ ID NO: LEAVAEEKPHVKPYFSK ENSG00000065534.14 7 772 SEQ ID NO: LEVDAIVNAANSSLLGGGGVDG ENSG00000133315.6 7 773 CIHR SEQ ID NO: LLHEMQIQHPTASLIAK ENSG00000146731.6 7 774 SEQ ID NO: LLVEELPLR ENSG00000198947.10 7 775 SEQ ID NO: LMNSQLVTTEK ENSG00000073849.10 7 776 SEQ ID NO: LSNPPSAGPIVVHCSAGAGR ENSG00000152894.10 7 777 SEQ ID NO: LSPSSTETTTLPGSPTTPSLSEK ENSG00000205277.5 7 778 SEQ ID NO: LSPSSTETTTLPGSPTTPSLSEK ENSG00000205277.5 7 779 SEQ ID NO: LSPSSTETTTLPGSPTTPSLSEK ENSG00000205277.5 7 780 SEQ ID NO: LSPSSTETTTLPGSPTTPSLSEK ENSG00000205277.5 7 781 SEQ ID NO: MYLFYGNK ENSG00000196961.8 7 782 SEQ ID NO: PPLLLILDR ENSG00000136631.8 7 783 SEQ ID NO: PSLSLGTITDEEMK ENSG00000137497.13 7 784 SEQ ID NO: QCHECIEHIR ENSG00000106066.9 7 785 SEQ ID NO: QQNQELQEQLR ENSG00000137497.13 7 786 SEQ ID NO: SFAPILPHLAEEVFQHIPY ENSG00000067704.8 7 787 SEQ ID NO: SGLCPHVVVLVATVR ENSG00000100714.11 7 788 SEQ ID NO: SITILSTPEGTSAACK ENSG00000136231.9 7 789 SEQ ID NO: SLEGSDDAVLLQR ENSG00000198947.10 7 790 SEQ ID NO: SMDAETYVEGQR ENSG00000130396.16 7 791 SEQ ID NO: STTSGLVGESTPSR ENSG00000205277.5 7 792 SEQ ID NO: STTSGLVGESTPSR ENSG00000205277.5 7 793 SEQ ID NO: STTSGLVGESTPSR ENSG00000205277.5 7 794 SEQ ID NO: STTSGLVGESTPSR ENSG00000205277.5 7 795 SEQ ID NO: TQGSSTSWFGSNQSKPEFTVDLK ENSG00000165322.13 7 796 SEQ ID NO: VIMIVTDGRPQDSVAEVAAK ENSG00000132561.9 7 797 SEQ ID NO: VPPPKPATPDFR ENSG00000065534.14 7 798 SEQ ID NO: WGFCPIK ENSG00000011028.9 7 799 SEQ ID NO: YAVQVAEGMGYLESKR ENSG00000061938.12 7 800 SEQ ID NO: AAEEIGIKATHIKLPR ENSG00000100714.11 6 801 SEQ ID NO: AGDAVNVVVTGGK ENSG00000132205.6 6 802 SEQ ID NO: AGDTLSGTCLLIANK ENSG00000142453.7 6 803 SEQ ID NO: AGDTLSGTCLLIANKR ENSG00000142453.7 6 804 SEQ ID NO: AIDYEIQR ENSG00000059691.7 6 805 SEQ ID NO: ALEQALEK ENSG00000166825.9 6 806 SEQ ID NO: ALSSAGER ENSG00000172037.9 6 807 SEQ ID NO: CFLCDSR ENSG00000172037.9 6 808 SEQ ID NO: DAEEWVQQLK ENSG00000005020.8 6 809 SEQ ID NO: DDEFTHLYTLIVRPDNTYEVK ENSG00000179218.9 6 810 SEQ ID NO: DFGSFDKFKEK ENSG00000112096.12 6 811 SEQ ID NO: DGDVQAGANLSFNR ENSG00000158560.10 6 812 SEQ ID NO: EFASHLQQLQDALNELTEEHSK ENSG00000137497.13 6 813 SEQ ID NO: ETLPELPSVTR ENSG00000059691.7 6 814 SEQ ID NO: GAPMHDLLLWNNATVTTCHSK ENSG00000100714.11 6 815 SEQ ID NO: HKSDFGK ENSG00000179218.9 6 816 SEQ ID NO: IALETSLSK ENSG00000076662.5 6 817 SEQ ID NO: IGDFGLMR ENSG00000061938.12 6 818 SEQ ID NO: ILREEGPK ENSG00000004864.9 6 819 SEQ ID NO: KSEAPFTHK ENSG00000162614.14 6 820 SEQ ID NO: LCGDLVSCFQER ENSG00000165912.11 6 821 SEQ ID NO: LLDLLEGLTGQK ENSG00000198947.10 6 822 SEQ ID NO: LLEQSIQSAQETEK ENSG00000198947.10 6 823 SEQ ID NO: LQAEDCSIACLPR ENSG00000152894.10 6 824 SEQ ID NO: MNVVFAVK ENSG00000136631.8 6 825 SEQ ID NO: NPPAAYIQK ENSG00000184922.9 6 826 SEQ ID NO: NTSLNPQELQR ENSG00000125826.15 6 827 SEQ ID NO: NVLINKDIR ENSG00000179218.9 6 828 SEQ ID NO: PAETLKPMGN ENSG00000065534.14 6 829 SEQ ID NO: PAETLKPMGN ENSG00000065534.14 6 830 SEQ ID NO: PFSLDALSK ENSG00000146731.6 6 831 SEQ ID NO: PLLPANHVTMAK ENSG00000067704.8 6 832 SEQ ID NO: PSGYTCACDSGFR ENSG00000090006.13 6 833 SEQ ID NO: PSVVLSAAHTVAAR ENSG00000032444.11 6 834 SEQ ID NO: QASNGVLIR ENSG00000166825.9 6 835 SEQ ID NO: QGLELAADCHLSR ENSG00000130396.16 6 836 SEQ ID NO: QVEELLMAMEK ENSG00000082805.15 6 837 SEQ ID NO: QVEKEETNEIQVVNEEPQR ENSG00000135052.12 6 838 SEQ ID NO: RLEAEFPPHHSQSTFR ENSG00000061938.12 6 839 SEQ ID NO: SWDTNLIECNLDQELK ENSG00000131711.10 6 840 SEQ ID NO: TGEPCVAELTEENFQR ENSG00000082805.15 6 841 SEQ ID NO: VECEPSWQPFQGHCYR ENSG00000011028.9 6 842 SEQ ID NO: VRFTPVVCGLR ENSG00000090006.13 6 843 SEQ ID NO: VSLSQPR ENSG00000090006.13 6 844 SEQ ID NO: AAEGYTQFYYVDVLDGK ENSG00000205277.5 5 845 SEQ ID NO: AALEEVEGDVAELELK ENSG00000114331.8 5 846 SEQ ID NO: AEEFGNETWGVTK ENSG00000179218.9 5 847 SEQ ID NO: AFEDWLNDDLGSYQGAQGNR ENSG00000101199.8 5 848 SEQ ID NO: ATQEWLEK ENSG00000137497.13 5 849 SEQ ID NO: CSQFCTTGMDGGMSIWDVK ENSG00000130429.8 5 850 SEQ ID NO: DQLVIPDGQEEEQEAAGEGR ENSG00000135052.12 5 851 SEQ ID NO: EAQEAEAFALYHK ENSG00000099991.12 5 852 SEQ ID NO: EGNCSGCIQDCNR ENSG00000104450.8 5 853 SEQ ID NO: EGQIQSVVTYDLALDSGRPHSR ENSG00000169896.12 5 854 SEQ ID NO: EIDAALQKK ENSG00000162614.14 5 855 SEQ ID NO: ERFQNLDKK ENSG00000130429.8 5 856 SEQ ID NO: ETQPPDLPTTALGGCPSDWIQFL ENSG00000011028.9 5 857 NK SEQ ID NO: FREFLESQEDYDPCWSLQEK ENSG00000101199.8 5 858 SEQ ID NO: GGTAAGAGLDSLHK ENSG00000130429.8 5 859 SEQ ID NO: GLNPGTLNILVR ENSG00000152894.10 5 860 SEQ ID NO: GQLAPVFQR ENSG00000213380.9 5 861 SEQ ID NO: GSAASTCILTIESK ENSG00000162614.14 5 862 SEQ ID NO: ICGVEDAVSEMTR ENSG00000146733.9 5 863 SEQ ID NO: IITEGFEAAKEK ENSG00000146731.6 5 864 SEQ ID NO: ILKDIANR ENSG00000067704.8 5 865 SEQ ID NO: IQDLEHHLGLALNEVQAAK ENSG00000011454.12 5 866 SEQ ID NO: IVDAVIEQVK ENSG00000170776.15 5 867 SEQ ID NO: KVNVLQK ENSG00000082805.15 5 868 SEQ ID NO: LLLQCQVSSDPPATIIWTLNGK ENSG00000065534.14 5 869 SEQ ID NO: LSFEEMER ENSG00000162614.14 5 870 SEQ ID NO: LSPIPAVPASVPLQAWHPAK ENSG00000104450.8 5 871 SEQ ID NO: NQDNEDEWPLAEILSVK ENSG00000172977.8 5 872 SEQ ID NO: PTTLTDEEINR ENSG00000100714.11 5 873 SEQ ID NO: QIIEDQSGHYIWVPSPEKL ENSG00000082458.7 5 874 SEQ ID NO: QIQESEHMK ENSG00000065534.14 5 875 SEQ ID NO: RDFGSFDK ENSG00000112096.12 5 876 SEQ ID NO: RPQLEELITAAQNLK ENSG00000198947.10 5 877 SEQ ID NO: RPYWCISR ENSG00000067704.8 5 878 SEQ ID NO: SEESTASHSSQDATGTIVLPAR ENSG00000205277.5 5 879 SEQ ID NO: SEESTASHSSQDATGTIVLPAR ENSG00000205277.5 5 880 SEQ ID NO: SEESTASHSSQDATGTIVLPAR ENSG00000205277.5 5 881 SEQ ID NO: SEESTASHSSQDATGTIVLPAR ENSG00000205277.5 5 882 SEQ ID NO: SGTIFDNFLITNDEAY ENSG00000179218.9 5 883 SEQ ID NO: SQDADSPGSSGAPENLTFK ENSG00000130396.16 5 884 SEQ ID NO: TCYPLESRPSLSLGTITDEEMK ENSG00000137497.13 5 885 SEQ ID NO: TGLFTPDMAFETIVK ENSG00000106976.14 5 886 SEQ ID NO: VATEAEFSPEDSPSVR ENSG00000155629.10 5 887 SEQ ID NO: VPPPCDLGR ENSG00000090006.13 5 888 SEQ ID NO: VVSNFILQALQGEPLTVYGSGSQ ENSG00000115652.10 5 889 TR SEQ ID NO: AAIVFTDGR ENSG00000132561.9 4 890 SEQ ID NO: AGKGEVTFEDVK ENSG00000004864.9 4 891 SEQ ID NO: AIDLEIK ENSG00000162614.14 4 892 SEQ ID NO: AIEEELQEIASEPTNK ENSG00000132561.9 4 893 SEQ ID NO: ASFITPVPGGVGPMTVAMLMQ ENSG00000100714.11 4 894 STVESAKR SEQ ID NO: CAVVSSAGSLK ENSG00000073849.10 4 895 SEQ ID NO: CHYYANK ENSG00000134871.13 4 896 SEQ ID NO: CLTALPYICK ENSG00000011028.9 4 897 SEQ ID NO: DEELPTLLHFAAK ENSG00000155629.10 4 898 SEQ ID NO: DKVMPLIIQGFK ENSG00000086475.10 4 899 SEQ ID NO: DKVVALAEGR ENSG00000101199.8 4 900 SEQ ID NO: DQVFGSNLANLCQR ENSG00000165322.13 4 901 SEQ ID NO: DVFNVEDQKR ENSG00000135052.12 4 902 SEQ ID NO: EAELEYNPEHVSR ENSG00000067704.8 4 903 SEQ ID NO: EATDVIIIHSK ENSG00000166825.9 4 904 SEQ ID NO: EQYDVPQEWR ENSG00000205277.5 4 905 SEQ ID NO: ESPQDSAITR ENSG00000011454.12 4 906 SEQ ID NO: EVVLQWFTENSK ENSG00000166825.9 4 907 SEQ ID NO: EYFTFPASK ENSG00000130396.16 4 908 SEQ ID NO: FFDSACTMGAYHPLLYEK ENSG00000073849.10 4 909 SEQ ID NO: FGSFDKFK ENSG00000112096.12 4 910 SEQ ID NO: FIEAGQFNDNLYGTSIQSVR ENSG00000082458.7 4 911 SEQ ID NO: FIPGSALNGMVEMMDR ENSG00000067704.8 4 912 SEQ ID NO: GHLQIAACPNQD ENSG00000112096.12 4 913 SEQ ID NO: GSWQPVGDLLIDSLQDHLEK ENSG00000198947.10 4 914 SEQ ID NO: HVVPGVER ENSG00000130589.12 4 915 SEQ ID NO: IDYGTGHEAAFAAFLCCLCK ENSG00000119383.15 4 916 SEQ ID NO: IVGNGSEQQLQK ENSG00000011454.12 4 917 SEQ ID NO: KESEETIIQTDEDVPGPVPVK ENSG00000152894.10 4 918 SEQ ID NO: LEPAGPACPEGGR ENSG00000213380.9 4 919 SEQ ID NO: LETLTNQFSDSK ENSG00000082805.15 4 920 SEQ ID NO: LFSGSQVR ENSG00000059691.7 4 921 SEQ ID NO: LLEILK ENSG00000082805.15 4 922 SEQ ID NO: LLQQFPLDLEK ENSG00000198947.10 4 923 SEQ ID NO: LLTESVNSVIAQAPPVAQEALKK ENSG00000198947.10 4 924 SEQ ID NO: LPVEDKIR ENSG00000100714.11 4 925 SEQ ID NO: LPYGGQCR ENSG00000172037.9 4 926 SEQ ID NO: LSTAITLLPLEEGR ENSG00000019144.12 4 927 SEQ ID NO: LTASSTCGLNGPQPYCIVSHLQD ENSG00000172037.9 4 928 EKK SEQ ID NO: LVTPHGESEQIGVIPSK ENSG00000082458.7 4 929 SEQ ID NO: NAEVRPPFTYASLIR ENSG00000114861.14 4 930 SEQ ID NO: PAETLKPMGNAKPDENLK ENSG00000065534.14 4 931 SEQ ID NO: PGGAGPCATVSVFPGAR ENSG00000142453.7 4 932 SEQ ID NO: QELNTIASKPPR ENSG00000169896.12 4 933 SEQ ID NO: RFSTEYELQQLEQFKK ENSG00000166825.9 4 934 SEQ ID NO: RVPPPCAPGR ENSG00000090006.13 4 935 SEQ ID NO: SCHAGFGSPAGWDVPVGALIQR ENSG00000163975.7 4 936 SEQ ID NO: SFGHFPGPEFLDVEK ENSG00000165322.13 4 937 SEQ ID NO: SITEVGEALK ENSG00000198947.10 4 938 SEQ ID NO: SLQADTTNTDTALTTLEEALAEKE ENSG00000082805.15 4 939 R SEQ ID NO: SSNLLDLKNPFFR ENSG00000142453.7 4 940 SEQ ID NO: TGYAFVDCPDESWALK ENSG00000136231.9 4 941 SEQ ID NO: TQVTFFFPLDLSYR ENSG00000169896.12 4 942 SEQ ID NO: TSKDDLLLTDFEGALK ENSG00000011454.12 4 943 SEQ ID NO: TVTINTEQK ENSG00000065534.14 4 944 SEQ ID NO: VADLLQHINLMK ENSG00000152894.10 4 945 SEQ ID NO: VDANISVHHPGEPLGVR ENSG00000059691.7 4 946 SEQ ID NO: VMVGDLEDINEMIIK ENSG00000198947.10 4 947 SEQ ID NO: VVGDVAYDEAKER ENSG00000100714.11 4 948 SEQ ID NO: VYLLYR ENSG00000167770.7 4 949 SEQ ID NO: WANGLSEEKPLSVPR ENSG00000064545.10 4 950 SEQ ID NO: WAPNENK ENSG00000130429.8 4 951 SEQ ID NO: WCVLSTPEIQK ENSG00000163975.7 4 952 SEQ ID NO: WMDPEGEMKPGR ENSG00000113387.7 4 953 SEQ ID NO: WVLLQDILLK ENSG00000198947.10 4 954 SEQ ID NO: YEEQRPSLK ENSG00000162614.14 4 955 SEQ ID NO: YGLLNVTK ENSG00000165322.13 4 956 SEQ ID NO: YQHIGLVAMFR ENSG00000169896.12 4 957 SEQ ID NO: YVPAIAHLIHSLNPVR ENSG00000106066.9 4 958 SEQ ID NO: AAILQTEVDALR ENSG00000082805.15 3 959 SEQ ID NO: ADGGPEAGELPSIGEATAALALA ENSG00000019144.12 3 960 GR SEQ ID NO: AENYWWR ENSG00000061938.12 3 961 SEQ ID NO: AEQPPHLTPGIR ENSG00000146733.9 3 962 SEQ ID NO: AIEALSGK ENSG00000136231.9 3 963 SEQ ID NO: AIGNIELGIR ENSG00000131711.10 3 964 SEQ ID NO: AMNNSWHPECFR ENSG00000169756.12 3 965 SEQ ID NO: APNLSSGNVSLK ENSG00000155629.10 3 966 SEQ ID NO: AQVAHADQQLR ENSG00000137497.13 3 967 SEQ ID NO: AREHFGTVK ENSG00000211460.7 3 968 SEQ ID NO: ARFEQMAKAREE ENSG00000162614.14 3 969 SEQ ID NO: ASFANEDGQVSPGSLLLAGAIAG ENSG00000004864.9 3 970 MPAASLVTPADVIK SEQ ID NO: AVVVGFDPHFSYMK ENSG00000184207.8 3 971 SEQ ID NO: DDLLLTDFEGALK ENSG00000011454.12 3 972 SEQ ID NO: DNEETGFGSGTR ENSG00000166825.9 3 973 SEQ ID NO: DVDGLTSINAGK ENSG00000100714.11 3 974 SEQ ID NO: EAGIQPSLLCVR ENSG00000163975.7 3 975 SEQ ID NO: EDFNSKHMANQRALGK ENSG00000172037.9 3 976 SEQ ID NO: EEGDLGPVYGFQWR ENSG00000176890.11 3 977 SEQ ID NO: EELSSGDSLSPDPWK ENSG00000130396.16 3 978 SEQ ID NO: ELQKAVEEMK ENSG00000198947.10 3 979 SEQ ID NO: ENSMLREEMHRRFENAPDSAKT ENSG00000082805.15 3 980 K SEQ ID NO: EQISDIDDAVRK ENSG00000113387.7 3 981 SEQ ID NO: EVVDAGLVGLER ENSG00000138162.13 3 982 SEQ ID NO: FEALQAPACHENMVK ENSG00000196961.8 3 983 SEQ ID NO: FHLCSVATR ENSG00000196961.8 3 984 SEQ ID NO: FNLDTENAMTFQENAR ENSG00000169896.12 3 985 SEQ ID NO: FTEEIPLK ENSG00000136231.9 3 986 SEQ ID NO: GALTSTPYSPTQHLER ENSG00000153310.14 3 987 SEQ ID NO: GDEGPIGHQGPIGQEGAPGR ENSG00000134871.13 3 988 SEQ ID NO: GDSGQPLFLTPYIEAGK ENSG00000106066.9 3 989 SEQ ID NO: GEPVSAEDLGVSGALTVLMK ENSG00000100714.11 3 990 SEQ ID NO: GFSGIFPACHPCHACFGDWDR ENSG00000172037.9 3 991 SEQ ID NO: GIDTPQCHR ENSG00000172037.9 3 992 SEQ ID NO: GWDSSHEDDLPVYLAR ENSG00000113657.8 3 993 SEQ ID NO: HEQNIDCGGGYV ENSG00000179218.9 3 994 SEQ ID NO: HLNQGTDEDIYLLGK ENSG00000073849.10 3 995 SEQ ID NO: IAELQQR ENSG00000137497.13 3 996 SEQ ID NO: ILVVITDGEK ENSG00000169896.12 3 997 SEQ ID NO: INDAFNLASAHK ENSG00000166825.9 3 998 SEQ ID NO: INLPAPNPDHVGGYK ENSG00000004864.9 3 999 SEQ ID NO: IQEILTQVK ENSG00000136231.9 3 1000 SEQ ID NO: IQPTTPSEPTAIK ENSG00000198947.10 3 1001 SEQ ID NO: ISPGSTEITTLPGSTTTPGLSEAST ENSG00000205277.5 3 1002 TFYSSPR SEQ ID NO: ISPGSTEITTLPGSTTTPGLSEAST ENSG00000205277.5 3 1003 TFYSSPR SEQ ID NO: ISPGSTEITTLPGSTTTPGLSEAST ENSG00000205277.5 3 1004 TFYSSPR SEQ ID NO: ISPGSTEITTLPGSTTTPGLSEAST ENSG00000205277.5 3 1005 TFYSSPR SEQ ID NO: ISSMERGLR ENSG00000082805.15 3 1006 SEQ ID NO: IVLDVGCGSGILSFFAAQAGAR ENSG00000142453.7 3 1007 SEQ ID NO: IYGADDIELLPEAQHKAEVYTK ENSG00000100714.11 3 1008 SEQ ID NO: KDVKLDK ENSG00000170776.15 3 1009 SEQ ID NO: KFQETEQTIQK ENSG00000132205.6 3 1010 SEQ ID NO: KFSYDLSQCINQMK ENSG00000135052.12 3 1011 SEQ ID NO: KLPAENGSSSAETLNAK ENSG00000065534.14 3 1012 SEQ ID NO: KLTELENELNTK ENSG00000130396.16 3 1013 SEQ ID NO: KQTENPK ENSG00000198947.10 3 1014 SEQ ID NO: KQVTPLFIHFR ENSG00000166825.9 3 1015 SEQ ID NO: KRVEDAYILTCNVSLEYEK ENSG00000146731.6 3 1016 SEQ ID NO: KVPFAWCAPESLK ENSG00000061938.12 3 1017 SEQ ID NO: LAGAPAPK ENSG00000184207.8 3 1018 SEQ ID NO: LHELYEKVFSRRADR ENSG00000032444.11 3 1019 SEQ ID NO: LLDPEDVDTTYPDKK ENSG00000198947.10 3 1020 SEQ ID NO: LLESLQENHFQEDEQFLGAVMP ENSG00000086475.10 3 1021 R SEQ ID NO: LLQVAVEDR ENSG00000198947.10 3 1022 SEQ ID NO: LLVSDIQTIQPSLNSVNEGGQK ENSG00000198947.10 3 1023 SEQ ID NO: LNLHSADWQR ENSG00000198947.10 3 1024 SEQ ID NO: LPAENGSSSAETLNAK ENSG00000065534.14 3 1025 SEQ ID NO: LPLEDADIIK ENSG00000110237.3 3 1026 SEQ ID NO: LPLQMALTELETLAEK ENSG00000104728.11 3 1027 SEQ ID NO: LPTEWNVLGTDQSLHDAGPR ENSG00000170776.15 3 1028 SEQ ID NO: LQEALSQLDFQWEK ENSG00000198947.10 3 1029 SEQ ID NO: LQEPSAQANCCDSEKNGDIGQQ ENSG00000132205.6 3 1030 IK SEQ ID NO: LQSQVISELDACKECTQGVQR ENSG00000132205.6 3 1031 SEQ ID NO: LYIGNLSENAAPSDLESIFK ENSG00000136231.9 3 1032 SEQ ID NO: MLESYLHAK ENSG00000142453.7 3 1033 SEQ ID NO: NLLLATR ENSG00000061938.12 3 1034 SEQ ID NO: NVLLHEMQIQHPTASLIAK ENSG00000146731.6 3 1035 SEQ ID NO: QKPCDLPLR ENSG00000136231.9 3 1036 SEQ ID NO: QPAAFIVTQYPLPNTVK ENSG00000152894.10 3 1037 SEQ ID NO: QQLGHIEAWAEK ENSG00000130396.16 3 1038 SEQ ID NO: QREEHYFCK ENSG00000133315.6 3 1039 SEQ ID NO: QVFHALEDELQK ENSG00000151914.13 3 1040 SEQ ID NO: QWMENPNNNPIHPNLR ENSG00000166825.9 3 1041 SEQ ID NO: SAQALVEQMVNEGVNADSIK ENSG00000198947.10 3 1042 SEQ ID NO: SATSVLVGEPTTSPISSGSTETTAL ENSG00000205277.5 3 1043 PGSTTTAGLSEK SEQ ID NO: SATSVLVGEPTTSPISSGSTETTAL ENSG00000205277.5 3 1044 PGSTTTAGLSEK SEQ ID NO: SATSVLVGEPTTSPISSGSTETTAL ENSG00000205277.5 3 1045 PGSTTTAGLSEK SEQ ID NO: SAVEGMPSNLDSEVAWGK ENSG00000198947.10 3 1046 SEQ ID NO: SEDSTIYDLLKDPVSLR ENSG00000104728.11 3 1047 SEQ ID NO: SLESALKDLK ENSG00000130429.8 3 1048 SEQ ID NO: SPNPALTFCVK ENSG00000019144.12 3 1049 SEQ ID NO: STTFYTSPR ENSG00000205277.5 3 1050 SEQ ID NO: STTFYTSPR ENSG00000205277.5 3 1051 SEQ ID NO: STTFYTSPR ENSG00000205277.5 3 1052 SEQ ID NO: STTFYTSPR ENSG00000205277.5 3 1053 SEQ ID NO: TCHYYANK ENSG00000134871.13 3 1054 SEQ ID NO: TCSECQELHWGDPGLQCHACDC ENSG00000172037.9 3 1055 DSR SEQ ID NO: TCYPLESR ENSG00000137497.13 3 1056 SEQ ID NO: TEFQLELPVK ENSG00000169896.12 3 1057 SEQ ID NO: TKEPVIMSTLETVR ENSG00000198947.10 3 1058 SEQ ID NO: TPLWIGLAGEEGSRR ENSG00000011028.9 3 1059 SEQ ID NO: TQSLNPAPFSPLTAQQMKPEKPS ENSG00000130396.16 3 1060 TLQRPQETVIR SEQ ID NO: TVGWNVPVGYLVESGR ENSG00000163975.7 3 1061 SEQ ID NO: VASSSSGNNFLSGSPASPMGDIL ENSG00000137497.13 3 1062 QTPQFQMR SEQ ID NO: VAWVSHDSTVCLADADK ENSG00000130429.8 3 1063 SEQ ID NO: VEQQPDYR ENSG00000130396.16 3 1064 SEQ ID NO: VIQEVSGLPSEGASEGNQYTPDA ENSG00000169129.10 3 1065 QR SEQ ID NO: VLDLLDPASGDLVIR ENSG00000079616.8 3 1066 SEQ ID NO: VLLHEMQIQHPTASLIAK ENSG00000146731.6 3 1067 SEQ ID NO: VMDKVTSDETR ENSG00000138162.13 3 1068 SEQ ID NO: VPRYELLLK ENSG00000127084.13 3 1069 SEQ ID NO: VQFGASHVFK ENSG00000130396.16 3 1070 SEQ ID NO: VSCIVSAAK ENSG00000169129.10 3 1071 SEQ ID NO: VTEILGIEPDREK ENSG00000211460.7 3 1072 SEQ ID NO: VVDALNQGLPR ENSG00000079616.8 3 1073 SEQ ID NO: WKTPAAIPATPVAVSQPIR ENSG00000130396.16 3 1074 SEQ ID NO: YLETADYAIREEIVLK ENSG00000196961.8 3 1075 SEQ ID NO: YLNWESDQPDNPSEENCGVIR ENSG00000011028.9 3 1076 SEQ ID NO: YVGFGNTPPPQKK ENSG00000101199.8 3 1077 SEQ ID NO: AAGNFATK ENSG00000130396.16 2 1078 SEQ ID NO: AEGERQPPPDSSEEAPPATQNFII ENSG00000119383.15 2 1079 PK SEQ ID NO: AGLVVEDALFETLPSDVR ENSG00000171488.10 2 1080 SEQ ID NO: AHCGDPVSLAAAGDGSPDIGPT ENSG00000127084.13 2 1081 GELSGSLK SEQ ID NO: AILQNHTDFKDK ENSG00000142453.7 2 1082 SEQ ID NO: AINVYGTSEPSQESELTTVGEKPE ENSG00000065534.14 2 1083 EPK SEQ ID NO: ALGEDQVAETSAMSDVLKDILK ENSG00000157617.12 2 1084 SEQ ID NO: ANIVMVLEIVSGGELFER ENSG00000065534.14 2 1085 SEQ ID NO: APEEQGLLPNGEPSQHSSAPQK ENSG00000169129.10 2 1086 SEQ ID NO: APGLGVLSPSGEER ENSG00000065534.14 2 1087 SEQ ID NO: AQDDVSEWASK ENSG00000132561.9 2 1088 SEQ ID NO: ASSISEEVAVGSIAATLK ENSG00000170776.15 2 1089 SEQ ID NO: ATLALDSVLTEEGK ENSG00000170776.15 2 1090 SEQ ID NO: AVGGDRQEAIQPGCIGGPKGLP ENSG00000134871.13 2 1091 GLPGPPGPTGAKGLRGIPGFAGA DGGP SEQ ID NO: AVGLVSTWTQR ENSG00000127084.13 2 1092 SEQ ID NO: AVSSADPR ENSG00000138162.13 2 1093 SEQ ID NO: AWHAFFTAAER ENSG00000165912.11 2 1094 SEQ ID NO: DCTQCLQHPWLMK ENSG00000065534.14 2 1095 SEQ ID NO: DEISDDAKDFISNLLK ENSG00000065534.14 2 1096 SEQ ID NO: DFGPASQHFLSTSVQGPWER ENSG00000198947.10 2 1097 SEQ ID NO: DFLDSLGFSTR ENSG00000176890.11 2 1098 SEQ ID NO: DGEWEPPVIQNPEYK ENSG00000179218.9 2 1099 SEQ ID NO: DTSPAPSGTTSAFVK ENSG00000205277.5 2 1100 SEQ ID NO: EAEDRARQEEERR ENSG00000130396.16 2 1101 SEQ ID NO: EAPYGAPR ENSG00000090006.13 2 1102 SEQ ID NO: ECAIYTNR ENSG00000104450.8 2 1103 SEQ ID NO: EGIVALRR ENSG00000146731.6 2 1104 SEQ ID NO: EGPYTVDAIQK ENSG00000198947.10 2 1105 SEQ ID NO: EKELQTIFDTLPPMR ENSG00000198947.10 2 1106 SEQ ID NO: ELEQQLQESAR ENSG00000019144.12 2 1107 SEQ ID NO: EQLDKIQSSHNFQLESVNK ENSG00000135052.12 2 1108 SEQ ID NO: EVTKEEFVLAAQK ENSG00000004864.9 2 1109 SEQ ID NO: EVVPGDSVNSLLSILDVITGHQHP ENSG00000032444.11 2 1110 QR SEQ ID NO: EYWMDPEGEMKPGRK ENSG00000113387.7 2 1111 SEQ ID NO: FGFSHLEALLDDSK ENSG00000167770.7 2 1112 SEQ ID NO: FGSQASQK ENSG00000101199.8 2 1113 SEQ ID NO: FHELTQTDK ENSG00000100714.11 2 1114 SEQ ID NO: FLDLGISIAENR ENSG00000125826.15 2 1115 SEQ ID NO: FLLDCGIR ENSG00000065534.14 2 1116 SEQ ID NO: FVDPSQDHALAK ENSG00000130396.16 2 1117 SEQ ID NO: FYGDEEK ENSG00000179218.9 2 1118 SEQ ID NO: GAWLGMNFNPK ENSG00000011028.9 2 1119 SEQ ID NO: GILVFQLK ENSG00000130396.16 2 1120 SEQ ID NO: GISLNPEQWSQL ENSG00000113387.7 2 1121 SEQ ID NO: GLYLPLFKPSVSTSK ENSG00000004864.9 2 1122 SEQ ID NO: GMEDLIPLVNR ENSG00000106976.14 2 1123 SEQ ID NO: GPIGHQGPIGQEGAPGR ENSG00000134871.13 2 1124 SEQ ID NO: GPNKHTLTQIK ENSG00000146731.6 2 1125 SEQ ID NO: GPTCNEFTGQCHCR ENSG00000172037.9 2 1126 SEQ ID NO: GSEGEPGIR ENSG00000134871.13 2 1127 SEQ ID NO: GTDVREPDDSPQGR ENSG00000011028.9 2 1128 SEQ ID NO: GWAGDSGPQGR ENSG00000134871.13 2 1129 SEQ ID NO: HAQEELPPPPPQKK ENSG00000198947.10 2 1130 SEQ ID NO: HSTVLENTDGK ENSG00000163975.7 2 1131 SEQ ID NO: IEELEEALR ENSG00000082805.15 2 1132 SEQ ID NO: IEGSGDQIDTYELSGGAR ENSG00000106976.14 2 1133 SEQ ID NO: IELHGKPIEVEHSVPK ENSG00000136231.9 2 1134 SEQ ID NO: IIDEDFELTERECIK ENSG00000065534.14 2 1135 SEQ ID NO: IKLIDFGLAR ENSG00000065534.14 2 1136 SEQ ID NO: ILDLLNEGSAR ENSG00000079616.8 2 1137 SEQ ID NO: ILMELDGPNWR ENSG00000104450.8 2 1138 SEQ ID NO: IPQAVVDVSSHLQK ENSG00000171488.10 2 1139 SEQ ID NO: IQAEQVDAVTLSGEDIYTAGK ENSG00000163975.7 2 1140 SEQ ID NO: IVIYVQQTTNK ENSG00000011454.12 2 1141 SEQ ID NO: IVSEFDYVEK ENSG00000166825.9 2 1142 SEQ ID NO: KADTLPR ENSG00000049323.11 2 1143 SEQ ID NO: KINQLSEENGDLSFK ENSG00000137497.13 2 1144 SEQ ID NO: KIQEILTQVK ENSG00000136231.9 2 1145 SEQ ID NO: KKLPAENGSSSAETLNAK ENSG00000065534.14 2 1146 SEQ ID NO: KLLLQCQVSSDPPATIIWTLNGK ENSG00000065534.14 2 1147 SEQ ID NO: KPAAGLSAAPVPTAPAAGAPL ENSG00000115310.13 2 1148 SEQ ID NO: KSPSSDSWTCADTSTER ENSG00000101199.8 2 1149 SEQ ID NO: KSSTGSPTSPLNAEK ENSG00000065534.14 2 1150 SEQ ID NO: LALLNEK ENSG00000137497.13 2 1151 SEQ ID NO: LDIDEK ENSG00000130396.16 2 1152 SEQ ID NO: LIAPLEGYTR ENSG00000167608.7 2 1153 SEQ ID NO: LKEEEEDKK ENSG00000179218.9 2 1154 SEQ ID NO: LKNQVTQLKEQVPGFTPR ENSG00000100714.11 2 1155 SEQ ID NO: LLDPQTNTEIANYPIYK ENSG00000011454.12 2 1156 SEQ ID NO: LLDRLPSFQQSCR ENSG00000213380.9 2 1157 SEQ ID NO: LLEAIKR ENSG00000112096.12 2 1158 SEQ ID NO: LLGFGSALLDNVDPNPENFVGA ENSG00000196961.8 2 1159 GIIQTK SEQ ID NO: LQAQLNELQAQLSQKEQAAEHY ENSG00000137497.13 2 1160 K SEQ ID NO: LQDVHVAEGKK ENSG00000065534.14 2 1161 SEQ ID NO: LQGEVLALEEER ENSG00000019144.12 2 1162 SEQ ID NO: LSALHLEVR ENSG00000165912.11 2 1163 SEQ ID NO: LSSQLVEHCQK ENSG00000198947.10 2 1164 SEQ ID NO: LSVMGCDVLK ENSG00000163975.7 2 1165 SEQ ID NO: LTAASVGVQGSGWGWLGFNKE ENSG00000112096.12 2 1166 R SEQ ID NO: LTDVAIGAPGEEDNR ENSG00000169896.12 2 1167 SEQ ID NO: LTHGVLHTK ENSG00000105223.14 2 1168 SEQ ID NO: LVTDPDSGLCSHYWGAIIR ENSG00000130396.16 2 1169 SEQ ID NO: MDPEGEMKPGR ENSG00000113387.7 2 1170 SEQ ID NO: MELLVK ENSG00000145362.12 2 1171 SEQ ID NO: MVSMMEGVIQK ENSG00000130396.16 2 1172 SEQ ID NO: MVVASSK ENSG00000100714.11 2 1173 SEQ ID NO: NDAGQAECSCQVTVDDAPASE ENSG00000065534.14 2 1174 NTKAPEMK SEQ ID NO: NILSEFQR ENSG00000198947.10 2 1175 SEQ ID NO: NLLEVSEVEQELACQNDHSSALQ ENSG00000136631.8 2 1176 NIK SEQ ID NO: NLVDSYMAIVNK ENSG00000106976.14 2 1177 SEQ ID NO: NVNVFFPHFK ENSG00000151116.12 2 1178 SEQ ID NO: PASAEQIQHLAGAIAER ENSG00000172037.9 2 1179 SEQ ID NO: PAVPASVPLQAWHPAK ENSG00000104450.8 2 1180 SEQ ID NO: PFSAIYFPCYAHVK ENSG00000004864.9 2 1181 SEQ ID NO: PGPVPAHSLCGHLVPK ENSG00000172037.9 2 1182 SEQ ID NO: PLQGTTGLIPLLGIDVWEHAYYL ENSG00000112096.12 2 1183 QYK SEQ ID NO: PNENKFAVGSGSR ENSG00000130429.8 2 1184 SEQ ID NO: PPVQFSLLHSK ENSG00000196961.8 2 1185 SEQ ID NO: QAPIGGDFPAVQK ENSG00000198947.10 2 1186 SEQ ID NO: QKLQDVHVAEGK ENSG00000065534.14 2 1187 SEQ ID NO: QLAAYIADKVDAAQMPQEAQK ENSG00000198947.10 2 1188 SEQ ID NO: QLSESSKLK ENSG00000157617.12 2 1189 SEQ ID NO: QQTANKVEIEK ENSG00000011454.12 2 1190 SEQ ID NO: QSSSSRDDNMFQIGK ENSG00000113387.7 2 1191 SEQ ID NO: QYTYGLVSCGLDR ENSG00000004139.9 2 1192 SEQ ID NO: RAGNSLAASTAEETAGSAQGR ENSG00000172037.9 2 1193 SEQ ID NO: REAPYGAPR ENSG00000090006.13 2 1194 SEQ ID NO: REPAPNAPGDIAAAFPAER ENSG00000138162.13 2 1195 SEQ ID NO: RGWDSSHEDDLPVYLAR ENSG00000113657.8 2 1196 SEQ ID NO: RLEEESAQLK ENSG00000011454.12 2 1197 SEQ ID NO: RQVEKEETNEIQVVNEEPQR ENSG00000135052.12 2 1198 SEQ ID NO: RSESQGTAPAFK ENSG00000065534.14 2 1199 SEQ ID NO: SCTEETHGFICQK ENSG00000011028.9 2 1200 SEQ ID NO: SDFGKFVLSSGK ENSG00000179218.9 2 1201 SEQ ID NO: SEYMEGNVR ENSG00000166825.9 2 1202 SEQ ID NO: SFAPILPHLAEEVFQHIPYIK ENSG00000067704.8 2 1203 SEQ ID NO: SKVPQETQSGGGSR ENSG00000049323.11 2 1204 SEQ ID NO: SPATTLSPASTTSSGVSEESTTSHS ENSG00000205277.5 2 1205 R SEQ ID NO: SPATTLSPASTTSSGVSEESTTSHS ENSG00000205277.5 2 1206 R SEQ ID NO: SPATTLSPASTTSSGVSEESTTSHS ENSG00000205277.5 2 1207 RPGSTHTTAFPDSTTTPGLSR SEQ ID NO: SPATTLSPASTTSSGVSEESTTSHS ENSG00000205277.5 2 1208 RPGSTHTTAFPDSTTTPGLSR SEQ ID NO: SQDLQVIDLLTVGESR ENSG00000169231.9 2 1209 SEQ ID NO: SREPQAKPQLDLSIDSLDLSCEEG ENSG00000137497.13 2 1210 TPLSITSK SEQ ID NO: SRQELASGLPSPAATQELPVER ENSG00000138162.13 2 1211 SEQ ID NO: SSAAAGAPSR ENSG00000049323.11 2 1212 SEQ ID NO: SSPNVANQPPSPGGK ENSG00000130396.16 2 1213 SEQ ID NO: SSSEVLVLAETLDGVR ENSG00000130589.12 2 1214 SEQ ID NO: SVQEIAEQLLLENHPAR ENSG00000151914.13 2 1215 SEQ ID NO: TCTGYHQVR ENSG00000133316.11 2 1216 SEQ ID NO: TGETSR ENSG00000113387.7 2 1217 SEQ ID NO: TIQNQLR ENSG00000169896.12 2 1218 SEQ ID NO: TLFSLMQYSEEFR ENSG00000169896.12 2 1219 SEQ ID NO: TPAPDGPR ENSG00000032444.11 2 1220 SEQ ID NO: TPGQIVSEK ENSG00000059691.7 2 1221 SEQ ID NO: TPVPEK ENSG00000065534.14 2 1222 SEQ ID NO: TTLLDPDSCR ENSG00000205277.5 2 1223 SEQ ID NO: TTTESEVMK ENSG00000100714.11 2 1224 SEQ ID NO: TVLQIDCGLQLANDSVNR ENSG00000104450.8 2 1225 SEQ ID NO: VAQQPLSLVGCEVVPDPSPDHLY ENSG00000169129.10 2 1226 SFR SEQ ID NO: VHALNNVNK ENSG00000198947.10 2 1227 SEQ ID NO: VIVMPTTK ENSG00000067704.8 2 1228 SEQ ID NO: VLQEDLEQEQVR ENSG00000198947.10 2 1229 SEQ ID NO: VPAHAVVVR ENSG00000163975.7 2 1230 SEQ ID NO: WLNEVEFK ENSG00000198947.10 2 1231 SEQ ID NO: WTDGSIINFISWAPGK ENSG00000011028.9 2 1232 SEQ ID NO: WTDGSIINFISWAPGKPR ENSG00000011028.9 2 1233 SEQ ID NO: WVNAQFSK ENSG00000198947.10 2 1234 SEQ ID NO: YDNFGVLGLDLWQVK ENSG00000179218.9 2 1235 SEQ ID NO: YLLYRPGHYDILYK ENSG00000167770.7 2 1236 SEQ ID NO: YLSSLDLLLEHR ENSG00000133315.6 2 1237 SEQ ID NO: YLVHCLQSELNNYMPAFLDDPEE ENSG00000130396.16 2 1238 NSLQRPK SEQ ID NO: YRDPGVLPWGALEEEEEDGGR ENSG00000167608.7 2 1239 SEQ ID NO: AAAAAVGPGAGGAGSAVPGGA ENSG00000142453.7 1 1240 GPCATVSVFPGAR SEQ ID NO: AAAKVALTKRADPAELR ENSG00000004864.9 1 1241 SEQ ID NO: AAATEEPEVIPDPAK ENSG00000152894.10 1 1242 SEQ ID NO: AAEEPQQQK ENSG00000167770.7 1 1243 SEQ ID NO: AAGDGSPDIGPTGELSGSLKIPNR ENSG00000127084.13 1 1244 SEQ ID NO: AAGLQAEIGQVK ENSG00000082805.15 1 1245 SEQ ID NO: AASGVPR ENSG00000155629.10 1 1246 SEQ ID NO: ACGNMFGLMHGTCPETSGGLLI ENSG00000086475.10 1 1247 CLPR SEQ ID NO: ADSAVSQEQLR ENSG00000165912.11 1 1248 SEQ ID NO: AEEKPHVKPYFSK ENSG00000065534.14 1 1249 SEQ ID NO: AELEYNPEHVSR ENSG00000067704.8 1 1250 SEQ ID NO: AEQLLQDAR ENSG00000172037.9 1 1251 SEQ ID NO: AEYMRIQAQQQATKPSKEMS ENSG00000017373.11 1 1252 SEQ ID NO: AFCGLGTTGMWR ENSG00000110237.3 1 1253 SEQ ID NO: AFLEAVAEEKPHVKPYFSK ENSG00000065534.14 1 1254 SEQ ID NO: AHKQCALKLLR ENSG00000141447.12 1 1255 SEQ ID NO: ALMDLLQLTR ENSG00000079616.8 1 1256 SEQ ID NO: ALQDFEEPDK ENSG00000061938.12 1 1257 SEQ ID NO: ALQFLEEVKVSR ENSG00000146731.6 1 1258 SEQ ID NO: ALQHMAAMSSAQIVSATAIHNK ENSG00000187079.10 1 1259 LGLPGIPRPT SEQ ID NO: AMAYETLEQYGK ENSG00000104450.8 1 1260 SEQ ID NO: AMLAAVLEQELPALAENLHQEQ ENSG00000142733.10 1 1261 K SEQ ID NO: AMLAAVLEQELPALAENLHQEQ ENSG00000142733.10 1 1262 K SEQ ID NO: ANGITMYAVGVGKAIEEELQEIA ENSG00000132561.9 1 1263 SEPTNK SEQ ID NO: APAPDVPGCSR ENSG00000172037.9 1 1264 SEQ ID NO: APILPHLAEEVFQHIPYIK ENSG00000067704.8 1 1265 SEQ ID NO: AQALLADVDTLLFDCDGVLWR ENSG00000184207.8 1 1266 SEQ ID NO: AQNSGFDLQETLVK ENSG00000146731.6 1 1267 SEQ ID NO: ARFEQMAK ENSG00000162614.14 1 1268 SEQ ID NO: ARPEAYQVPASYQPDEEER ENSG00000125826.15 1 1269 SEQ ID NO: ARTSAGVGAWGAAAVGRTAGV ENSG00000133315.6 1 1270 R SEQ ID NO: ASIPLKELEQFNSDIQK ENSG00000198947.10 1 1271 SEQ ID NO: ATSCFPRPMTPRDR ENSG00000137497.13 1 1272 SEQ ID NO: AVTSVSGPGEHLR ENSG00000169231.9 1 1273 SEQ ID NO: CAEVVSGK ENSG00000067704.8 1 1274 SEQ ID NO: CFGLLLSPGK ENSG00000011454.12 1 1275 SEQ ID NO: CGDSDKGFVVINQK ENSG00000146731.6 1 1276 SEQ ID NO: CGGLSCNGAAATADLALGR ENSG00000172037.9 1 1277 SEQ ID NO: CLCPPDFAGK ENSG00000090006.13 1 1278 SEQ ID NO: CLQHPWLMK ENSG00000065534.14 1 1279 SEQ ID NO: CLVENAGDVAFVR ENSG00000163975.7 1 1280 SEQ ID NO: CSGNIDPMDPDACDPHTGQCLR ENSG00000172037.9 1 1281 SEQ ID NO: CTEGPIDLVFVIDGSK ENSG00000132561.9 1 1282 SEQ ID NO: CTQCLQHPWLMK ENSG00000065534.14 1 1283 SEQ ID NO: CVRWAPNENK ENSG00000130429.8 1 1284 SEQ ID NO: DALLEALK ENSG00000172037.9 1 1285 SEQ ID NO: DCCFEISAPDKR ENSG00000005020.8 1 1286 SEQ ID NO: DDRTGTGTLSVFGMQARYSLR ENSG00000176890.11 1 1287 SEQ ID NO: DEDFELTERECIK ENSG00000065534.14 1 1288 SEQ ID NO: DISLQGPGLAPE ENSG00000019144.12 1 1289 SEQ ID NO: DITAALAAER ENSG00000106976.14 1 1290 SEQ ID NO: DLNVISSLLK ENSG00000225485.3 1 1291 SEQ ID NO: DQREPLPPAPAENEMK ENSG00000104728.11 1 1292 SEQ ID NO: DQSPLVSSSDSPPRPQPAFK ENSG00000115310.13 1 1293 SEQ ID NO: DRRGSGKPR ENSG00000130396.16 1 1294 SEQ ID NO: DSSHAFTLDELR ENSG00000163975.7 1 1295 SEQ ID NO: DWDSPYSHDLDTSADSVGNACR ENSG00000105223.14 1 1296 SEQ ID NO: EAEQLLRGPLGDQYQTVK ENSG00000172037.9 1 1297 SEQ ID NO: EAEVQTWLQQIGFSK ENSG00000004139.9 1 1298 SEQ ID NO: EDTVQSVK ENSG00000106066.9 1 1299 SEQ ID NO: EEAEQVLGQAR ENSG00000198947.10 1 1300 SEQ ID NO: EGIVALR ENSG00000146731.6 1 1301 SEQ ID NO: EGTEAEPLPLR ENSG00000142733.10 1 1302 SEQ ID NO: EGTEAEPLPLR ENSG00000142733.10 1 1303 SEQ ID NO: EGTPGIFQK ENSG00000205277.5 1 1304 SEQ ID NO: EGVIQNFK ENSG00000130396.16 1 1305 SEQ ID NO: EIDAALQK ENSG00000162614.14 1 1306 SEQ ID NO: EIHTVPDMGKWKR ENSG00000119383.15 1 1307 SEQ ID NO: EKLTAASVGVQGSGWGWLGFN ENSG00000112096.12 1 1308 K SEQ ID NO: ELEAKMLAQKAEEKENHCPTML ENSG00000079616.8 1 1309 R SEQ ID NO: ELEEKDGDVQAGANLSFNR ENSG00000158560.10 1 1310 SEQ ID NO: ELETLTTNYQWLCTR ENSG00000198947.10 1 1311 SEQ ID NO: ELLLSGPPEVAAPDTPYLHVDSA ENSG00000138162.13 1 1312 AQR SEQ ID NO: ELQDGIGQR ENSG00000198947.10 1 1313 SEQ ID NO: EMSKKAPSEISRK ENSG00000198947.10 1 1314 SEQ ID NO: ENIRQEISIMNCLHHPK ENSG00000065534.14 1 1315 SEQ ID NO: EPMKAPLCGEGDQPGGFESQEK ENSG00000138162.13 1 1316 SEQ ID NO: EPYAREMLAISFISAVNR ENSG00000225485.3 1 1317 SEQ ID NO: ERARKFSGSGLAMGLGSASASA ENSG00000082458.7 1 1318 WRR SEQ ID NO: ERARKFSGSGLAMGLGSASASA ENSG00000082458.7 1 1319 WRR SEQ ID NO: ERVLSLSQALATEASQWHR ENSG00000105559.7 1 1320 SEQ ID NO: ESGRGSSTPPGPIAALGMPDTGP ENSG00000127084.13 1 1321 GSSSLGK SEQ ID NO: ESGSLEDDWDFLPPKK ENSG00000179218.9 1 1322 SEQ ID NO: EVARNVFECNDQVVK ENSG00000169896.12 1 1323 SEQ ID NO: EVPEEGPGAPAR ENSG00000186635.10 1 1324 SEQ ID NO: EYQEDLALR ENSG00000125826.15 1 1325 SEQ ID NO: FAGDSLK ENSG00000151914.13 1 1326 SEQ ID NO: FGPGDQVR ENSG00000114331.8 1 1327 SEQ ID NO: FGVLGLDLWQVK ENSG00000179218.9 1 1328 SEQ ID NO: FKDNPTVVVEDLR ENSG00000114331.8 1 1329 SEQ ID NO: FNGAPTANFQQDVGTK ENSG00000073849.10 1 1330 SEQ ID NO: FNHPAEAKWMK ENSG00000019144.12 1 1331 SEQ ID NO: FNRALNCMNLPPDK ENSG00000184922.9 1 1332 SEQ ID NO: FRLAEDGKR ENSG00000132561.9 1 1333 SEQ ID NO: FSAEALR ENSG00000073849.10 1 1334 SEQ ID NO: FSPEVPGQK ENSG00000131711.10 1 1335 SEQ ID NO: FTDFEEVR ENSG00000106976.14 1 1336 SEQ ID NO: FVPIIGIAMPLSSR ENSG00000151835.9 1 1337 SEQ ID NO: FWPAIDDGLRR ENSG00000105223.14 1 1338 SEQ ID NO: FWVVDQTHFYLGSANMDWR ENSG00000105223.14 1 1339 SEQ ID NO: GAAVDEYFRQPVVDTFDIR ENSG00000142453.7 1 1340 SEQ ID NO: GAFHRPVLGGFR ENSG00000165912.11 1 1341 SEQ ID NO: GAGLAWGVHDCQLCSER ENSG00000090006.13 1 1342 SEQ ID NO: GAPISAYQIVVEELHPHRT ENSG00000152894.10 1 1343 SEQ ID NO: GATGHPGGGQGAENPAGLKSQ ENSG00000104450.8 1 1344 GNELFR SEQ ID NO: GCLELIKETGVPIAGR ENSG00000100714.11 1 1345 SEQ ID NO: GCPQEDSDIAFLIDGSGSIIPHDF ENSG00000169896.12 1 1346 R SEQ ID NO: GDEGPIGHQGPIGQEGAPGRPG ENSG00000134871.13 1 1347 SPGLPGMPGR SEQ ID NO: GDKGERGAPGVTGPK ENSG00000134871.13 1 1348 SEQ ID NO: GDNVLINTFSGLLK ENSG00000142733.10 1 1349 SEQ ID NO: GDNVLINTFSGLLK ENSG00000142733.10 1 1350 SEQ ID NO: GDTGNPGAPGTPGTKGWAGDS ENSG00000134871.13 1 1351 GPQGRP SEQ ID NO: GEFAIDGYSVR ENSG00000005020.8 1 1352 SEQ ID NO: GEGLYADPYGLLHEGR ENSG00000017373.11 1 1353 SEQ ID NO: GEIAPLKENVSHVNDLAR ENSG00000198947.10 1 1354 SEQ ID NO: GEWKPRQIDNPDYK ENSG00000179218.9 1 1355 SEQ ID NO: GGCVALATGSAMGLWEVK ENSG00000011028.9 1 1356 SEQ ID NO: GGHDIILAAFDNFK ENSG00000184922.9 1 1357 SEQ ID NO: GGSQPPDIDKTELVEPTEYLVVHL ENSG00000166825.9 1 1358 K SEQ ID NO: GGVSAVPGFR ENSG00000134871.13 1 1359 SEQ ID NO: GHLQIAACPNQDPLQGTTGLIPL ENSG00000112096.12 1 1360 LGIDVWEHAY SEQ ID NO: GHPDRLPLQMALTELETLAEK ENSG00000104728.11 1 1361 SEQ ID NO: GKEAGEVR ENSG00000169896.12 1 1362 SEQ ID NO: GKNVLINKDIR ENSG00000179218.9 1 1363 SEQ ID NO: GLCFLFGSNLR ENSG00000169896.12 1 1364 SEQ ID NO: GLEEAVESACAMR ENSG00000067704.8 1 1365 SEQ ID NO: GLGKYICQKCHAIIDEQPL ENSG00000169756.12 1 1366 SEQ ID NO: GNCFCYGHASECAPAPGAPAHA ENSG00000172037.9 1 1367 EGMVHGACICK SEQ ID NO: GPAPARPKMLVISGGDGYEDFRL ENSG00000110237.3 1 1368 SSGGGSSS SEQ ID NO: GPGAGSALDDGRR ENSG00000196961.8 1 1369 SEQ ID NO: GPPSSVPK ENSG00000184922.9 1 1370 SEQ ID NO: GQLQDELEKGER ENSG00000082805.15 1 1371 SEQ ID NO: GQTPEAGADKRSPRRASAAAAA ENSG00000104450.8 1 1372 GGGATGHPGG SEQ ID NO: GREPASCEDLCGGGVGADGGGS ENSG00000065534.14 1 1373 DR SEQ ID NO: GRISVSLQEEASGGSLAAPAR ENSG00000032444.11 1 1374 SEQ ID NO: GSDGMDAVRSAPTLIR ENSG00000150672.12 1 1375 SEQ ID NO: GSRPGIEGDTPR ENSG00000113657.8 1 1376 SEQ ID NO: GTISFFEIDGR ENSG00000172977.8 1 1377 SEQ ID NO: GTWIHPEIDNPEYSPD ENSG00000179218.9 1 1378 SEQ ID NO: GVTDTLAQIR ENSG00000017373.11 1 1379 SEQ ID NO: GWDCHGLPIEIK ENSG00000067704.8 1 1380 SEQ ID NO: HCELCRPFFYR ENSG00000172037.9 1 1381 SEQ ID NO: HFQIDYDEDGNCSLIISDVCGDD ENSG00000065534.14 1 1382 DAK SEQ ID NO: HGGLSLVQTTDYIYPIVDDPYM ENSG00000086475.10 1 1383 MGR SEQ ID NO: HLDTLHNFVSR ENSG00000151914.13 1 1384 SEQ ID NO: HLNPGLQLYR ENSG00000114331.8 1 1385 SEQ ID NO: HTEILEILEIPQLMDTCVR ENSG00000213380.9 1 1386 SEQ ID NO: HTLTQIKDAVR ENSG00000146731.6 1 1387 SEQ ID NO: IAALNASSTIEDDHEGSFK ENSG00000099991.12 1 1388 SEQ ID NO: IAEIQAR ENSG00000152894.10 1 1389 SEQ ID NO: IDALREELMEGMDR ENSG00000132205.6 1 1390 SEQ ID NO: IFEEQPCLRK ENSG00000099991.12 1 1391 SEQ ID NO: IFLTEQPLEGLEK ENSG00000198947.10 1 1392 SEQ ID NO: IFSAYIK ENSG00000130429.8 1 1393 SEQ ID NO: IIDRIHGTEEGQQILK ENSG00000137497.13 1 1394 SEQ ID NO: ILHKGEELAK ENSG00000169129.10 1 1395 SEQ ID NO: INELENGGEILNETRSFHHK ENSG00000059691.7 1 1396 SEQ ID NO: IPASAEQIQHLAGAIAER ENSG00000172037.9 1 1397 SEQ ID NO: IQGTLQPH ENSG00000172037.9 1 1398 SEQ ID NO: IQNQWDEVQEHLQNR ENSG00000198947.10 1 1399 SEQ ID NO: IQNVVTSFAPQRRAAWWQSEN ENSG00000172037.9 1 1400 GIPA SEQ ID NO: IRQKVDDCERCR ENSG00000011454.12 1 1401 SEQ ID NO: ITEQEKLK ENSG00000151914.13 1 1402 SEQ ID NO: ITSVSTGNLCTEEQTPPPRPEAYPI ENSG00000130396.16 1 1403 PTQTYTR SEQ ID NO: IVLGGTTVHNTK ENSG00000136631.8 1 1404 SEQ ID NO: IVTTHIR ENSG00000106976.14 1 1405 SEQ ID NO: KDAEGILEDLQSYR ENSG00000153310.14 1 1406 SEQ ID NO: KDVEVTKEEFVLAAQK ENSG00000004864.9 1 1407 SEQ ID NO: KEADMQQK ENSG00000158560.10 1 1408 SEQ ID NO: KHPSSPECLVSAQK ENSG00000137497.13 1 1409 SEQ ID NO: KIQNHIQTLK ENSG00000198947.10 1 1410 SEQ ID NO: KISEESGETAKRR ENSG00000099991.12 1 1411 SEQ ID NO: KIYAVEASTMAQHAEVLVK ENSG00000142453.7 1 1412 SEQ ID NO: KKEELNAVR ENSG00000198947.10 1 1413 SEQ ID NO: KKGPGAGSALDDGR ENSG00000196961.8 1 1414 SEQ ID NO: KLMQIR ENSG00000151914.13 1 1415 SEQ ID NO: KLSSQLVEHCQK ENSG00000198947.10 1 1416 SEQ ID NO: KLTFEYR ENSG00000119383.15 1 1417 SEQ ID NO: KMEEEPLGPDLEDLKR ENSG00000198947.10 1 1418 SEQ ID NO: KMSGTVSK ENSG00000136631.8 1 1419 SEQ ID NO: KQVAPEKPVKK ENSG00000113387.7 1 1420 SEQ ID NO: KSSTGSPTSPLNAEKLESEEDVSQ ENSG00000065534.14 1 1421 AF SEQ ID NO: KTRPDGNCFYR ENSG00000167770.7 1 1422 SEQ ID NO: KVSTLQNQR ENSG00000169896.12 1 1423 SEQ ID NO: LAGEEEALR ENSG00000125826.15 1 1424 SEQ ID NO: LCDNIVSESESTTAR ENSG00000170776.15 1 1425 SEQ ID NO: LCIEHVEEHGLDIDGIYR ENSG00000165322.13 1 1426 SEQ ID NO: LCQFEEAKQDCDQALQLADGNV ENSG00000104450.8 1 1427 K SEQ ID NO: LDAWEEAQVEFMASHGNDAAR ENSG00000105963.9 1 1428 SEQ ID NO: LDEDLTTLGQMSK ENSG00000110237.3 1 1429 SEQ ID NO: LDLFEISQPTEDLEFHGVMR ENSG00000130396.16 1 1430 SEQ ID NO: LEAIKR ENSG00000112096.12 1 1431 SEQ ID NO: LEMLQQIANR ENSG00000151914.13 1 1432 SEQ ID NO: LESEEDVSQAFLEAVAEEKPHVK ENSG00000065534.14 1 1433 SEQ ID NO: LESEEDVSQAFLEAVAEEKPHVK ENSG00000065534.14 1 1434 PY SEQ ID NO: LETMARNEVIADINCK ENSG00000141447.12 1 1435 SEQ ID NO: LEYNVDAANGIVMEGYLFK ENSG00000114331.8 1 1436 SEQ ID NO: LFPNSLDQTDMHGDSEYNIMFG ENSG00000179218.9 1 1437 PDICGPGTKK SEQ ID NO: LGCTMSMR ENSG00000059691.7 1 1438 SEQ ID NO: LGIEKTDPTTLTDEEINR ENSG00000100714.11 1 1439 SEQ ID NO: LGIVNVDEAVLHFK ENSG00000155629.10 1 1440 SEQ ID NO: LGYTPLIVACHYGNVK ENSG00000145362.12 1 1441 SEQ ID NO: LHEMQIQHPTASLIAK ENSG00000146731.6 1 1442 SEQ ID NO: LHYNELGAK ENSG00000198947.10 1 1443 SEQ ID NO: LKAVQAQGGESQQEAQR ENSG00000137497.13 1 1444 SEQ ID NO: LKEDMKKIVAVPLNEQK ENSG00000138640.10 1 1445 SEQ ID NO: LKEEEEDKKR ENSG00000179218.9 1 1446 SEQ ID NO: LKELNDWLTK ENSG00000198947.10 1 1447 SEQ ID NO: LKLSFEEMER ENSG00000162614.14 1 1448 SEQ ID NO: LKLTFEELER ENSG00000162614.14 1 1449 SEQ ID NO: LKPEIQCVSAK ENSG00000163975.7 1 1450 SEQ ID NO: LLEATPTDSCGYFR ENSG00000142733.10 1 1451 SEQ ID NO: LLEATPTDSCGYFR ENSG00000142733.10 1 1452 SEQ ID NO: LLKGESALQR ENSG00000114331.8 1 1453 SEQ ID NO: LLNEGQR ENSG00000163975.7 1 1454 SEQ ID NO: LNGFQLENFTLK ENSG00000136231.9 1 1455 SEQ ID NO: LNKILK ENSG00000067704.8 1 1456 SEQ ID NO: LNREVAESPRPR ENSG00000019144.12 1 1457 SEQ ID NO: LPPSSPQKLADVAAPPGGPPPPH ENSG00000017373.11 1 1458 SPYSGPPSR SEQ ID NO: LQDAFSAIGQNADLDLPQIAVVG ENSG00000106976.14 1 1459 GQSAGK SEQ ID NO: LQELEGTYEENERALESK ENSG00000172037.9 1 1460 SEQ ID NO: LQQQCDDYGSSYLGVIELIGEK ENSG00000132205.6 1 1461 SEQ ID NO: LSAHTHTLSLTDINELVCGAPGD ENSG00000172037.9 1 1462 APCATSPCGGAGCR SEQ ID NO: LSFEEMERQRR ENSG00000162614.14 1 1463 SEQ ID NO: LSGWLAQQEDAHR ENSG00000032444.11 1 1464 SEQ ID NO: LSHFEYVKNEDLEK ENSG00000061938.12 1 1465 SEQ ID NO: LSIPQLSVTDYEIM ENSG00000198947.10 1 1466 SEQ ID NO: LSIPQLSVTDYEIMEQR ENSG00000198947.10 1 1467 SEQ ID NO: LSPAYSLGSLTGASPCQSPCVQR ENSG00000019144.12 1 1468 SEQ ID NO: LSSGGGSSSETVGR ENSG00000110237.3 1 1469 SEQ ID NO: LTEEQCLFSAWLSEKEDAVNK ENSG00000198947.10 1 1470 SEQ ID NO: LVAAGGLDAVLYWCR ENSG00000004139.9 1 1471 SEQ ID NO: LVEFSAFLEQQR ENSG00000187079.10 1 1472 SEQ ID NO: LVPSVNGVR ENSG00000100714.11 1 1473 SEQ ID NO: LVTPHGESEQIGVIPSKK ENSG00000082458.7 1 1474 SEQ ID NO: LVVTQEDVELAYQEAMMNMAR ENSG00000086475.10 1 1475 LNRTAAGLMH SEQ ID NO: MAAAEAGGDDAR ENSG00000184207.8 1 1476 SEQ ID NO: MAVWEAEQLGGLQR ENSG00000130589.12 1 1477 SEQ ID NO: MEALENR ENSG00000132561.9 1 1478 SEQ ID NO: MEFDEKELRR ENSG00000106976.14 1 1479 SEQ ID NO: MESGRGSSTPPGPIAALGMPDT ENSG00000127084.13 1 1480 GPG SEQ ID NO: MESGRGSSTPPGPIAALGMPDT ENSG00000127084.13 1 1481 GPGSSSLGK SEQ ID NO: MESQLK ENSG00000082805.15 1 1482 SEQ ID NO: MGMSFGLESGK ENSG00000114126.13 1 1483 SEQ ID NO: MGNAAGSAEQPAGPAAPPPK ENSG00000184922.9 1 1484 SEQ ID NO: MIISTPQRLTSSGSVLIGSPYTPAP ENSG00000114126.13 1 1485 AMVTQTHIA SEQ ID NO: MILTNPEGR ENSG00000152894.10 1 1486 SEQ ID NO: MKAAKSGTKDGLEK ENSG00000074964.12 1 1487 SEQ ID NO: MLEDLGFKDLTLQPR ENSG00000125826.15 1 1488 SEQ ID NO: MNSLTLNR ENSG00000213380.9 1 1489 SEQ ID NO: MSDKSDLKAELER ENSG00000158560.10 1 1490 SEQ ID NO: MSGSSGGAAAPAASSGPAAAAS ENSG00000038382.13 1 1491 AAGSGCGGGA SEQ ID NO: MSKSLGNVIHP ENSG00000067704.8 1 1492 SEQ ID NO: MVSTSATDEPR ENSG00000032444.11 1 1493 SEQ ID NO: NANSSPVASTTPSASATTNPASA ENSG00000166825.9 1 1494 TTLDQSKA SEQ ID NO: NATLVNEADKLR ENSG00000166825.9 1 1495 SEQ ID NO: NAVLEHMEELQEQVALLTER ENSG00000184922.9 1 1496 SEQ ID NO: NDKSYWLSTTAPLPMMPVAEDE ENSG00000134871.13 1 1497 IKPYISR SEQ ID NO: NFVKEAEEISSNRR ENSG00000213380.9 1 1498 SEQ ID NO: NILVSDMEMNEQQE ENSG00000011028.9 1 1499 SEQ ID NO: NLAATLQDIETK ENSG00000019144.12 1 1500 SEQ ID NO: NLEELYLVGSLSHDISR ENSG00000171488.10 1 1501 SEQ ID NO: NLLEVSEVEQELACQNDHSSALQ ENSG00000136631.8 1 1502 NIKR SEQ ID NO: NLVGSGSEIQFLSEAQDDPQKR ENSG00000115652.10 1 1503 SEQ ID NO: NRTEAEVKR ENSG00000169129.10 1 1504 SEQ ID NO: NSLSVLSPK ENSG00000171488.10 1 1505 SEQ ID NO: NTSAASTAQLVEATEELRR ENSG00000172037.9 1 1506 SEQ ID NO: NVQVFLISGGFR ENSG00000146733.9 1 1507 SEQ ID NO: NYPSSLCALCVGDEQGR ENSG00000163975.7 1 1508 SEQ ID NO: PCPCPEGPGSQR ENSG00000172037.9 1 1509 SEQ ID NO: PCQDVDECAR ENSG00000090006.13 1 1510 SEQ ID NO: PDENLKSASKEELKK ENSG00000065534.14 1 1511 SEQ ID NO: PEAYQVPASYQPDEEERAR ENSG00000125826.15 1 1512 SEQ ID NO: PEGEMKPGR ENSG00000113387.7 1 1513 SEQ ID NO: PETPYSGPGLLIDSLVLLPR ENSG00000172037.9 1 1514 SEQ ID NO: PEVVWFK ENSG00000065534.14 1 1515 SEQ ID NO: PGAGAVEVAMAEALIK ENSG00000146731.6 1 1516 SEQ ID NO: PGEMGPQGPPGEPGFRGAPGK ENSG00000134871.13 1 1517 SEQ ID NO: PGETPSWTGSGFVR ENSG00000172037.9 1 1518 SEQ ID NO: PGFHGQAAR ENSG00000172037.9 1 1519 SEQ ID NO: PGHVGQMGPVGAPGRPGPPGP ENSG00000134871.13 1 1520 PGPK SEQ ID NO: PILPHLAEEVFQHIPYIK ENSG00000067704.8 1 1521 SEQ ID NO: PKIDDVLHTLTGAMSLLRR ENSG00000130396.16 1 1522 SEQ ID NO: PKMLVISGGDGYEDFR ENSG00000110237.3 1 1523 SEQ ID NO: PPDIDKTELVEPTEYLVVHLK ENSG00000166825.9 1 1524 SEQ ID NO: PPKPATPDFR ENSG00000065534.14 1 1525 SEQ ID NO: PPVIQNPEYK ENSG00000179218.9 1 1526 SEQ ID NO: PPVLGTESDATVK ENSG00000065534.14 1 1527 SEQ ID NO: PQLLGVAPEK ENSG00000004864.9 1 1528 SEQ ID NO: PRMSAQEQLERMR ENSG00000105559.7 1 1529 SEQ ID NO: PSGPATAEDPGRRPVLPQR ENSG00000132205.6 1 1530 SEQ ID NO: PTPRPVPMKRHIFR ENSG00000186635.10 1 1531 SEQ ID NO: PVAGSELPR ENSG00000176890.11 1 1532 SEQ ID NO: PYWCISR ENSG00000067704.8 1 1533 SEQ ID NO: QAASPLEPK ENSG00000137497.13 1 1534 SEQ ID NO: QAEEVNTEWEK ENSG00000198947.10 1 1535 SEQ ID NO: QAEGLSEDGAAMAVEPTQIQLS ENSG00000198947.10 1 1536 K SEQ ID NO: QAPSSFQLLYDLK ENSG00000100714.11 1 1537 SEQ ID NO: QAQLEKELSAALQDKK ENSG00000137497.13 1 1538 SEQ ID NO: QAQVNLTVVDKPD ENSG00000065534.14 1 1539 SEQ ID NO: QDCDQALQLADGNVK ENSG00000104450.8 1 1540 SEQ ID NO: QEMVIEVKAIGGKK ENSG00000110237.3 1 1541 SEQ ID NO: QETPPPRSPPVANSGSTGFSRRG ENSG00000105559.7 1 1542 SGRGGGPTP SEQ ID NO: QGPMTQAINR ENSG00000170776.15 1 1543 SEQ ID NO: QHEVEEATNILTATR ENSG00000114331.8 1 1544 SEQ ID NO: QIASLTGLVQSALLR ENSG00000017373.11 1 1545 SEQ ID NO: QICSQLSER ENSG00000011454.12 1 1546 SEQ ID NO: QKASGDSAR ENSG00000004864.9 1 1547 SEQ ID NO: QKMEEEKRRTEEER ENSG00000162614.14 1 1548 SEQ ID NO: QLELACETQEEVDSWK ENSG00000106976.14 1 1549 SEQ ID NO: QLNETGGPVLVSAPISPEEQDKL ENSG00000198947.10 1 1550 ENK SEQ ID NO: QLPKPNQDTMQILFR ENSG00000165322.13 1 1551 SEQ ID NO: QLQTLAPK ENSG00000105223.14 1 1552 SEQ ID NO: QNGDSAYLYLLSAR ENSG00000125826.15 1 1553 SEQ ID NO: QPDVEEILSK ENSG00000198947.10 1 1554 SEQ ID NO: QQNLAVSESPVTPSALAELLDLLD ENSG00000059691.7 1 1555 SR SEQ ID NO: QQQMHIVDMLSK ENSG00000130396.16 1 1556 SEQ ID NO: QSSHNFQLESVNK ENSG00000135052.12 1 1557 SEQ ID NO: QTLLAESEALTSYSHR ENSG00000167608.7 1 1558 SEQ ID NO: QTSVADLLASFNDQSTSDYLVVY ENSG00000167770.7 1 1559 LR SEQ ID NO: QVFGQTTIHQHIPFNWDSEFVQ ENSG00000004864.9 1 1560 LHFGK SEQ ID NO: QVVQDLLK ENSG00000141447.12 1 1561 SEQ ID NO: RASAAAAAGGGATGHPGGGQG ENSG00000104450.8 1 1562 AENPAGLK SEQ ID NO: RCDLCAPGYYGFGPTGCQACQC ENSG00000172037.9 1 1563 SHEGALSSLCEK SEQ ID NO: RCEQVQPGYFR ENSG00000172037.9 1 1564 SEQ ID NO: RDNEVDGQDYHFVVSR ENSG00000082458.7 1 1565 SEQ ID NO: RDPSSNDINGGMEPTPSTVSTPS ENSG00000196961.8 1 1566 PSADLLGLR SEQ ID NO: REMAAASAAAISGAGR ENSG00000079616.8 1 1567 SEQ ID NO: RETLFTLDDQALGPELTAPAPEPP ENSG00000213380.9 1 1568 AEEPR SEQ ID NO: RFSTEYELQQLEQFK ENSG00000166825.9 1 1569 SEQ ID NO: RGSDELTVPRYR ENSG00000017373.11 1 1570 SEQ ID NO: RIEGSGDQIDTYELSGGAR ENSG00000106976.14 1 1571 SEQ ID NO: RKEEEEAEDK ENSG00000179218.9 1 1572 SEQ ID NO: RLDIDEKPLVVQLNWNKDDR ENSG00000130396.16 1 1573 SEQ ID NO: RPPEPEKAPPAAPTRPSALELK ENSG00000184922.9 1 1574 SEQ ID NO: RPRPQGRSVSEPR ENSG00000125744.7 1 1575 SEQ ID NO: RQAEGLSEDGAAMAVEPTQIQL ENSG00000198947.10 1 1576 SK SEQ ID NO: RRKVPPSGSGGSELSNGEAGEAY ENSG00000110237.3 1 1577 R SEQ ID NO: RSLELQTRTEEEKK ENSG00000127084.13 1 1578 SEQ ID NO: RSSYLLAITTERSK ENSG00000225485.3 1 1579 SEQ ID NO: RVAAQVDGGAQVQQVLNIECLR ENSG00000196961.8 1 1580 SEQ ID NO: SAEESDRLR ENSG00000130396.16 1 1581 SEQ ID NO: SCDCDPMGSQDGGR ENSG00000172037.9 1 1582 SEQ ID NO: SDVLETVVLINPSDEAVSTEVR ENSG00000131711.10 1 1583 SEQ ID NO: SEDYELLCPNGAR ENSG00000163975.7 1 1584 SEQ ID NO: SFGSSLMESEVNLDR ENSG00000198947.10 1 1585 SEQ ID NO: SGHDQVVELLLERGAPLLAR ENSG00000145362.12 1 1586 SEQ ID NO: SGLTSLHLAAQEDKVNVADILTK ENSG00000145362.12 1 1587 SEQ ID NO: SGRPSCLYSAARPSGSYR ENSG00000124831.14 1 1588 SEQ ID NO: SGTIFDNFLITNDEA ENSG00000179218.9 1 1589 SEQ ID NO: SGTLALVEPLVASLDPGR ENSG00000004139.9 1 1590 SEQ ID NO: SKIVGAPMHDLLLWNNATVTTC ENSG00000100714.11 1 1591 HSK SEQ ID NO: SKPEDWDER ENSG00000179218.9 1 1592 SEQ ID NO: SLEGSDDAVLLQRRLDNMNFKW ENSG00000198947.10 1 1593 SELR SEQ ID NO: SLNPEQWSQLK ENSG00000113387.7 1 1594 SEQ ID NO: SLSDPSRRGELAGPGFEGPGGEP ENSG00000110237.3 1 1595 IREV SEQ ID NO: SNRDELELELAENR ENSG00000137497.13 1 1596 SEQ ID NO: SPARPQPGEGPGGPGGPPEVSR ENSG00000105559.7 1 1597 SEQ ID NO: SPARPQPGEGPGGPGGPPEVSR ENSG00000105559.7 1 1598 SEQ ID NO: SPDTTLSPASTTSSGVSEESTTSHS ENSG00000205277.5 1 1599 R SEQ ID NO: SPDTTLSPASTTSSGVSEESTTSHS ENSG00000205277.5 1 1600 R SEQ ID NO: SPDTTLSPASTTSSGVSEESTTSHS ENSG00000205277.5 1 1601 R SEQ ID NO: SPFPSQHLEAPEDK ENSG00000198947.10 1 1602 SEQ ID NO: SPGPPQVDGTPTMSLERPPR ENSG00000155629.10 1 1603 SEQ ID NO: SPTTTLSPASMTSLGVGEESTTSR ENSG00000205277.5 1 1604 SEQ ID NO: SPTTTLSPASMTSLGVGEESTTSR ENSG00000205277.5 1 1605 SEQ ID NO: SPTTTLSPASMTSLGVGEESTTSR ENSG00000205277.5 1 1606 SEQ ID NO: SPTTTLSPASMTSLGVGEESTTSR ENSG00000205277.5 1 1607 SEQ ID NO: SQAYADYIGFILTLNEGVK ENSG00000119383.15 1 1608 SEQ ID NO: SQMNCNLGTCQLQR ENSG00000205277.5 1 1609 SEQ ID NO: SRQELNTIASKPPR ENSG00000169896.12 1 1610 SEQ ID NO: SSHVTIDTLK ENSG00000163975.7 1 1611 SEQ ID NO: SSQNDSPGDASEGPEYLAIGNLD ENSG00000145016.9 1 1612 PRGR SEQ ID NO: STEYELQQLEQFKK ENSG00000166825.9 1 1613 SEQ ID NO: STSFNVQDLLPDHEYKFR ENSG00000065534.14 1 1614 SEQ ID NO: SVEQEVVQSQLNHCVNLYK ENSG00000198947.10 1 1615 SEQ ID NO: SVYTMPLANHR ENSG00000090006.13 1 1616 SEQ ID NO: SWAEDEKQKAETVQAALEEAQR ENSG00000172037.9 1 1617 SEQ ID NO: SWCSGHLHLRCPR ENSG00000032444.11 1 1618 SEQ ID NO: SYVDTGGVSR ENSG00000184922.9 1 1619 SEQ ID NO: SYVITGSWNPK ENSG00000011454.12 1 1620 SEQ ID NO: TAIWEDQNLR ENSG00000205277.5 1 1621 SEQ ID NO: TALLTAGDIYLLSTFR ENSG00000169231.9 1 1622 SEQ ID NO: TEALMDAQKEDFNSK ENSG00000172037.9 1 1623 SEQ ID NO: TEFCLHDGPPYANGDPHVGHAL ENSG00000067704.8 1 1624 NK SEQ ID NO: TESSGGWQNR ENSG00000011028.9 1 1625 SEQ ID NO: THIESSGHGVDTCLHVVLSSKVC ENSG00000019144.12 1 1626 R SEQ ID NO: TKVHAELADVLTEAVVDSILAIKK ENSG00000146731.6 1 1627 SEQ ID NO: TLEIALEQKKEECLK ENSG00000082805.15 1 1628 SEQ ID NO: TLNATGEEIIQQSSK ENSG00000198947.10 1 1629 SEQ ID NO: TLPSMVHR ENSG00000101199.8 1 1630 SEQ ID NO: TMNGDMR ENSG00000120549.11 1 1631 SEQ ID NO: TNHIGWVQEFLNEENR ENSG00000184922.9 1 1632 SEQ ID NO: TNIQLPACLR ENSG00000213380.9 1 1633 SEQ ID NO: TPDELQK ENSG00000198947.10 1 1634 SEQ ID NO: TPLERDDLHESVFR ENSG00000151914.13 1 1635 SEQ ID NO: TSGNQDEILVIR ENSG00000106976.14 1 1636 SEQ ID NO: TTLSPASSTSPGLQGESTAFQTHP ENSG00000205277.5 1 1637 ASTHTTPSPPSTATAPVEESTTYH R SEQ ID NO: TTLSPASSTSPGLQGESTAFQTHP ENSG00000205277.5 1 1638 ASTHTTPSPPSTATAPVEESTTYH R SEQ ID NO: TTLSPASSTSPGLQGESTAFQTHP ENSG00000205277.5 1 1639 ASTHTTPSPPSTATAPVEESTTYH R SEQ ID NO: TTQGLTALLLSLKK ENSG00000136631.8 1 1640 SEQ ID NO: TTQIINITMTK ENSG00000137497.13 1 1641 SEQ ID NO: TWVQQSETK ENSG00000198947.10 1 1642 SEQ ID NO: VAIGPSVLNAAR ENSG00000067704.8 1 1643 SEQ ID NO: VAYIPDEMAAQQNPLQQPR ENSG00000136231.9 1 1644 SEQ ID NO: VDSDMNDAYLGYAAAIILR ENSG00000169896.12 1 1645 SEQ ID NO: VEDAYILTCNVSLEYEK ENSG00000146731.6 1 1646 SEQ ID NO: VGAPMHDLLLWNNATVTTCHS ENSG00000100714.11 1 1647 K SEQ ID NO: VHLFDIITQYR ENSG00000213380.9 1 1648 SEQ ID NO: VIECFNVESR ENSG00000104728.11 1 1649 SEQ ID NO: VLGHFEKPLFLELCR ENSG00000032444.11 1 1650 SEQ ID NO: VLMDLQNQK ENSG00000198947.10 1 1651 SEQ ID NO: VLTTSPSR ENSG00000019144.12 1 1652 SEQ ID NO: VMLPPGAQHSDEK ENSG00000130396.16 1 1653 SEQ ID NO: VNFRPRYVTRYKTVTQLEWRCCP ENSG00000132205.6 1 1654 GFRGGDCQEGPK SEQ ID NO: VPDMAEIQSR ENSG00000032444.11 1 1655 SEQ ID NO: VQLLSQYDNEK ENSG00000184922.9 1 1656 SEQ ID NO: VSRASSPEGRHLPSPQLGTK ENSG00000105559.7 1 1657 SEQ ID NO: VTCTGYHQVR ENSG00000133316.11 1 1658 SEQ ID NO: VTEFDAAR ENSG00000136631.8 1 1659 SEQ ID NO: VVQEENQHMQMTIQALQDELR ENSG00000082805.15 1 1660 SEQ ID NO: VYLDLTPVK ENSG00000169129.10 1 1661 SEQ ID NO: WCATSDPEQHK ENSG00000163975.7 1 1662 SEQ ID NO: WFSIQNNQLVYQK ENSG00000114331.8 1 1663 SEQ ID NO: WIEFCQLLSER ENSG00000198947.10 1 1664 SEQ ID NO: WYQNPDYNFFNNYK ENSG00000073849.10 1 1665 SEQ ID NO: YADSLKPNIPYK ENSG00000130396.16 1 1666 SEQ ID NO: YENHSATAESSR ENSG00000152894.10 1 1667 SEQ ID NO: YLITATLTPER ENSG00000132205.6 1 1668 SEQ ID NO: YLQQPGCLLVGTNMDNR ENSG00000184207.8 1 1669 SEQ ID NO: YLRELSGSGLER ENSG00000213380.9 1 1670 SEQ ID NO: YLSASEYGSSVDGHPEVPETK ENSG00000169129.10 1 1671 SEQ ID NO: YNASSQQQR ENSG00000165322.13 1 1672 SEQ ID NO: YQETMSAIR ENSG00000198947.10 1 1673 SEQ ID NO: YSFWLTTIPEQSFQGSPSADTLK ENSG00000134871.13 1 1674 SEQ ID NO: YTKQGFGNLPICMAK ENSG00000100714.11 1 1675 SEQ ID NO: YVPAIAHLIHSLN ENSG00000106066.9 1 1676 SEQ ID NO: AAECLDVDECHRVPPPCDLGR ENSG00000090006.13 0 1677 SEQ ID NO: AEGGKRPAR ENSG00000104450.8 0 1678 SEQ ID NO: AEPVWTPPAPAPAAPPSTPAAP ENSG00000115310.13 0 1679 K SEQ ID NO: AFLCPLICHNGGVCVKPDR ENSG00000090006.13 0 1680 SEQ ID NO: AHLIHSLNPVR ENSG00000106066.9 0 1681 SEQ ID NO: AIAHLIHSLNPVR ENSG00000106066.9 0 1682 SEQ ID NO: AIWNVINW ENSG00000112096.12 0 1683 SEQ ID NO: AIWNVINWENV ENSG00000112096.12 0 1684 SEQ ID NO: ANGITMYAVGVGK ENSG00000132561.9 0 1685 SEQ ID NO: AQPVPFVPQVLGVMIGAGVAVV ENSG00000032444.11 0 1686 VTAVLILLVVRR SEQ ID NO: ARILTAAR ENSG00000004139.9 0 1687 SEQ ID NO: AVGPGAGGAGSAVPGGAGPCA ENSG00000142453.7 0 1688 TVSVFPGAR SEQ ID NO: AYDNFGVLGLDLWQVK ENSG00000179218.9 0 1689 SEQ ID NO: CVCPAGFR ENSG00000090006.13 0 1690 SEQ ID NO: CVHGPTGSR ENSG00000090006.13 0 1691 SEQ ID NO: CVPPRTSAGTFPGSQPQAPASPV ENSG00000090006.13 0 1692 LPAR SEQ ID NO: DHPSSHSAQPPR ENSG00000138162.13 0 1693 SEQ ID NO: DKERLQAMMTHLHVKSTEPK ENSG00000114861.14 0 1694 SEQ ID NO: DLDNAEEKADALNK ENSG00000011454.12 0 1695 SEQ ID NO: DLYSALIQFFQIFPEYK ENSG00000106066.9 0 1696 SEQ ID NO: DPASDKLLGPAGLTWERNLPGA ENSG00000138162.13 0 1697 GVGKEMAGVPPTLR SEQ ID NO: DSAVMDDSVVIPSHQVSTLAK ENSG00000145362.12 0 1698 SEQ ID NO: DSSTPYQEIAAVPSAGR ENSG00000138162.13 0 1699 SEQ ID NO: DWDSPYSHDLDT ENSG00000105223.14 0 1700 SEQ ID NO: DWDSPYSHDLDTS ENSG00000105223.14 0 1701 SEQ ID NO: EDLDQSPLVSSSDSPPRPQPAFK ENSG00000115310.13 0 1702 SEQ ID NO: EESREPAPASPAPA ENSG00000113657.8 0 1703 SEQ ID NO: ELSSKGVK ENSG00000176890.11 0 1704 SEQ ID NO: EMELRRQALEEERR ENSG00000019144.12 0 1705 SEQ ID NO: ENGTVPK ENSG00000165322.13 0 1706 SEQ ID NO: ENKEVVLQWFTENSK ENSG00000166825.9 0 1707 SEQ ID NO: EVAESPRPR ENSG00000019144.12 0 1708 SEQ ID NO: FILDNLK ENSG00000151835.9 0 1709 SEQ ID NO: FLEAVAEEKPHVKPYFSK ENSG00000065534.14 0 1710 SEQ ID NO: FPIEGGQKDPK ENSG00000107957.12 0 1711 SEQ ID NO: FSTEYELQQLEQFKKDNEETGFG ENSG00000166825.9 0 1712 SGTR SEQ ID NO: FWPAIDDGLR ENSG00000105223.14 0 1713 SEQ ID NO: FYIDFGGVKPMGSEPVPKSR ENSG00000004864.9 0 1714 SEQ ID NO: GADLIEEAASRIVDAVIEQVKAAG ENSG00000170776.15 0 1715 ALLTEGE SEQ ID NO: GADYAEPTWNLK ENSG00000166825.9 0 1716 SEQ ID NO: GDEEKDKGLQTSQDAR ENSG00000179218.9 0 1717 SEQ ID NO: GDILQTPQFQMR ENSG00000137497.13 0 1718 SEQ ID NO: GDNLPQYR ENSG00000205277.5 0 1719 SEQ ID NO: GNEAVASR ENSG00000135052.12 0 1720 SEQ ID NO: GPNKHTLTQIKDAVR ENSG00000146731.6 0 1721 SEQ ID NO: GQGPMFLDADFVAFTNHFK ENSG00000198947.10 0 1722 SEQ ID NO: GTATPELHTATDYR ENSG00000170776.15 0 1723 SEQ ID NO: GWAGDSGPQGRPGVFGLPGEK ENSG00000134871.13 0 1724 SEQ ID NO: GYLAPSGDLSLRR ENSG00000090006.13 0 1725 SEQ ID NO: HAEQQALR ENSG00000142453.7 0 1726 SEQ ID NO: IEDPSLLNSR ENSG00000032444.11 0 1727 SEQ ID NO: IFMEEVPGGSLSSLLRS ENSG00000142733.10 0 1728 SEQ ID NO: IFMEEVPGGSLSSLLRS ENSG00000142733.10 0 1729 SEQ ID NO: IIEVAPQVATQNVNPTPGAT ENSG00000086475.10 0 1730 SEQ ID NO: ILNSDQTTCR ENSG00000132561.9 0 1731 SEQ ID NO: ISCWGHSEPSMR ENSG00000105223.14 0 1732 SEQ ID NO: IVVHSVENMNFR ENSG00000184922.9 0 1733 SEQ ID NO: KAVAHMK ENSG00000132561.9 0 1734 SEQ ID NO: KDITAALAAER ENSG00000106976.14 0 1735 SEQ ID NO: KDNEETGFGSGTR ENSG00000166825.9 0 1736 SEQ ID NO: KHQGHFLLGTLSR ENSG00000061938.12 0 1737 SEQ ID NO: KIAEIQARR ENSG00000152894.10 0 1738 SEQ ID NO: KKEADMQQK ENSG00000158560.10 0 1739 SEQ ID NO: KLFGGPGSRR ENSG00000110237.3 0 1740 SEQ ID NO: KPAAGLSAAPVPTAPAAGAP ENSG00000115310.13 0 1741 SEQ ID NO: KSSTGSPTSPLNAEKLESEEDVSQ ENSG00000065534.14 0 1742 A SEQ ID NO: KVVATTQMQAADARK ENSG00000166825.9 0 1743 SEQ ID NO: LADSDQASKVQQQK ENSG00000137497.13 0 1744 SEQ ID NO: LAYVSCVR ENSG00000032444.11 0 1745 SEQ ID NO: LGIVQGIVGARNTSAASTAQLVE ENSG00000172037.9 0 1746 ATEELRREIG SEQ ID NO: LHYNELGAKVTERKQQ ENSG00000198947.10 0 1747 SEQ ID NO: LIEVGPSGAQFLGK ENSG00000145362.12 0 1748 SEQ ID NO: LKQTNLQWIK ENSG00000198947.10 0 1749 SEQ ID NO: LKTVFYR ENSG00000104728.11 0 1750 SEQ ID NO: LLISCWGHSEPSMR ENSG00000105223.14 0 1751 SEQ ID NO: LMFDRSEVYGPMK ENSG00000166825.9 0 1752 SEQ ID NO: LMLEWQFQK ENSG00000130396.16 0 1753 SEQ ID NO: LPAAPPVAPER ENSG00000115310.13 0 1754 SEQ ID NO: LPPVLGTESDATVK ENSG00000065534.14 0 1755 SEQ ID NO: LPQEPGR ENSG00000135052.12 0 1756 SEQ ID NO: LQGQDSERVRAWQR ENSG00000165912.11 0 1757 SEQ ID NO: LSRKGGHER ENSG00000019144.12 0 1758 SEQ ID NO: LTELENELNTK ENSG00000130396.16 0 1759 SEQ ID NO: LTGKAEGGK ENSG00000104450.8 0 1760 SEQ ID NO: LWEAVKRR ENSG00000061938.12 0 1761 SEQ ID NO: LWHLDPDTEYEIR ENSG00000152894.10 0 1762 SEQ ID NO: LYGVVLTPPMK ENSG00000061938.12 0 1763 SEQ ID NO: MELEEVTRLLNLKDK ENSG00000104450.8 0 1764 SEQ ID NO: MIEDSGPGMKVLL ENSG00000136631.8 0 1765 SEQ ID NO: MPVAGSELPR ENSG00000176890.11 0 1766 SEQ ID NO: NFVLVLSPGALDK ENSG00000004139.9 0 1767 SEQ ID NO: NIMFGPDICGPGTK ENSG00000179218.9 0 1768 SEQ ID NO: NITIIVEDPIAESCNDKAKLRGPL ENSG00000145016.9 0 1769 SEQ ID NO: NPKAEVARAQAALAVNISAARG ENSG00000146731.6 0 1770 LQDVLRTNLGPK SEQ ID NO: NQVTQLK ENSG00000100714.11 0 1771 SEQ ID NO: NVINWENVTER ENSG00000112096.12 0 1772 SEQ ID NO: PGHYDILYK ENSG00000167770.7 0 1773 SEQ ID NO: PGSPGLPGMPGR ENSG00000134871.13 0 1774 SEQ ID NO: PLEEGLNKAIHYFR ENSG00000115652.10 0 1775 SEQ ID NO: PLSTRVPR ENSG00000132561.9 0 1776 SEQ ID NO: PSAGFLPTHR ENSG00000090006.13 0 1777 SEQ ID NO: PSGPQPQADLQALLQSGAQVR ENSG00000105223.14 0 1778 SEQ ID NO: PSSSGSTGTKLSPARSTTSGLVGE ENSG00000205277.5 0 1779 STPSR SEQ ID NO: PSSSGSTGTKLSPARSTTSGLVGE ENSG00000205277.5 0 1780 STPSR SEQ ID NO: QGYILNSDQTTCR ENSG00000132561.9 0 1781 SEQ ID NO: QVFEELWK ENSG00000059691.7 0 1782 SEQ ID NO: QVKPKTVSEEERKV ENSG00000065534.14 0 1783 SEQ ID NO: QYISKMIEDSGPGMK ENSG00000136631.8 0 1784 SEQ ID NO: QYMPWEAALSSLSYFK ENSG00000166825.9 0 1785 SEQ ID NO: RADVLAFPSSGFTDLAEIVSR ENSG00000032444.11 0 1786 SEQ ID NO: RAVAAQPGRKR ENSG00000172977.8 0 1787 SEQ ID NO: RDEGSQDQTGSLSRARPSSR ENSG00000110237.3 0 1788 SEQ ID NO: RDPEVGKDELSKPSSDAESR ENSG00000138162.13 0 1789 SEQ ID NO: RMQSSADLIIQEFMDLRTR ENSG00000151914.13 0 1790 SEQ ID NO: SASFEPFSNK ENSG00000179218.9 0 1791 SEQ ID NO: SDQIGLPDFNAGAMENWGLVT ENSG00000166825.9 0 1792 YR SEQ ID NO: SFACQCPEGHVLR ENSG00000132561.9 0 1793 SEQ ID NO: SFLKLILQVEKWQEECEEGEGRTI ENSG00000152894.10 0 1794 IHCLNGGGR SEQ ID NO: SFPAAQIPIAVEEPGSSSRESVSK ENSG00000138162.13 0 1795 AGMPVSADAAK SEQ ID NO: SFTQGEGAR ENSG00000132561.9 0 1796 SEQ ID NO: SFTQGEGARPLSTR ENSG00000132561.9 0 1797 SEQ ID NO: SHTLSHASYLR ENSG00000145362.12 0 1798 SEQ ID NO: SLEQLQK ENSG00000137497.13 0 1799 SEQ ID NO: SPHTTLSPAGSTTR ENSG00000205277.5 0 1800 SEQ ID NO: SPHTTLSPAGSTTR ENSG00000205277.5 0 1801 SEQ ID NO: SPHTTLSPAGSTTR ENSG00000205277.5 0 1802 SEQ ID NO: SPHTTLSPAGSTTR ENSG00000205277.5 0 1803 SEQ ID NO: SQTLIDLNR ENSG00000059691.7 0 1804 SEQ ID NO: SSHNFQLESVNK ENSG00000135052.12 0 1805 SEQ ID NO: STCAPSPQR ENSG00000138162.13 0 1806 SEQ ID NO: STTFYSSPR ENSG00000205277.5 0 1807 SEQ ID NO: STTFYSSPR ENSG00000205277.5 0 1808 SEQ ID NO: STTFYSSPR ENSG00000205277.5 0 1809 SEQ ID NO: STTFYSSPR ENSG00000205277.5 0 1810 SEQ ID NO: STTFYSSPR ENSG00000205277.5 0 1811 SEQ ID NO: STTFYSSPR ENSG00000205277.5 0 1812 SEQ ID NO: STTFYSSPR ENSG00000205277.5 0 1813 SEQ ID NO: STTFYSSPR ENSG00000205277.5 0 1814 SEQ ID NO: STTFYSSPR ENSG00000205277.5 0 1815 SEQ ID NO: TATAGAISELTESRLR ENSG00000128487.12 0 1816 SEQ ID NO: TEVAIGPSVLNAAR ENSG00000067704.8 0 1817 SEQ ID NO: TGDPQETLRR ENSG00000137497.13 0 1818 SEQ ID NO: THLSLSHNPEQKGVPTGFILPIRDI ENSG00000100714.11 0 1819 R SEQ ID NO: THTATGIR ENSG00000169896.12 0 1820 SEQ ID NO: TLATQLNQQK ENSG00000151914.13 0 1821 SEQ ID NO: TPVPEKVPPPKPATPDF ENSG00000065534.14 0 1822 SEQ ID NO: TVQQPTVQHR ENSG00000132561.9 0 1823 SEQ ID NO: TYQGFWNPPLAPR ENSG00000152894.10 0 1824 SEQ ID NO: VLCGDAGLLRGLADGLVQAGVG ENSG00000142733.10 0 1825 TEALLTPLVGRLARL SEQ ID NO: VLCGDAGLLRGLADGLVQAGVG ENSG00000142733.10 0 1826 TEALLTPLVGRLARL SEQ ID NO: VNYDEENWRK ENSG00000166825.9 0 1827 SEQ ID NO: VPEGFTCR ENSG00000090006.13 0 1828 SEQ ID NO: WSELRKKSLNIR ENSG00000198947.10 0 1829 SEQ ID NO: WSSRGSGGWGVYRSPSFGAGE ENSG00000110237.3 0 1830 GLLR SEQ ID NO: WYQPSFHGVDLSALR ENSG00000142453.7 0 1831 SEQ ID NO: YCNPGDVCYYASR ENSG00000134871.13 0 1832 SEQ ID NO: YGNLGHVNIGAIQEPLAFILPK ENSG00000213380.9 0 1833 SEQ ID NO: YITISGNR ENSG00000151914.13 0 1834 SEQ ID NO: YLSYTLNPDLIRK ENSG00000166825.9 0 1835 SEQ ID NO: YMVTER ENSG00000105223.14 0 1836

To examine possible functions of somatic promoters on cancer development, we focused on RASA3, a RAS GTPase-activating protein required for G_(αi)-induced inhibition of mitogen-activated protein kinases. In both GCs (50%) and GC lines, we observed gain of promoter activity at an intronic region 127 kb downstream apart from the canonical RASA3 TSS (FIG. 3c , top, FIG. 10). RNA-seq and 5′ RACE analysis confirmed expression of this shorter RASA3 isoform (FIG. 3c , bottom), and expression of this shorter RASA3 isoform was also observed in TCGA RNA-seq data (FIG. 3c ). Compared to the canonical full-length RASA3 protein (CanT), the shorter 31 kDa RASA3 somatic isoform (SomT) is predicted to lack the N-terminal RasGAP domain (FIG. 3d ). Consistent with these predictions, transection of RASA3 CanT into GES1 normal gastric epithelial cells induced lower levels of active GTP-bound RAS compared to either empty vector or RASA3 SomT transfected cells, indicating that RASA3 CanT has higher RASGAP activity (FIG. 13).

To address functions of RASA3 SomT, we transfected the RASA3 CanT and SomT isoforms into SNU1967 GC cells. Compared to untransfected cells, transfection of RASA3 SomT into SNU1967 cells significantly stimulated migration (P<0.01) and invasion (P<0.01) while RASA3 CanT significantly suppressed invasion (P<0.001) (FIG. 3E, FIG. 13). Similarly, transfection of RASA3 SomT into GES1 cells significantly stimulated migration (p<0.01, FIG. 3e ) and invasion (P<0.01, FIG. 13) while RASA3 CanT did not. When tested on KRAS mutated AGS GC cells that are innately highly migratory, expression of RASA3 CanT potently suppressed migration while RASA3 SomT exhibited significantly less attenuation (P<0.01, FIG. 13). These results suggest that tumor-specific use of RASA3 SomT is likely to increase GC cell migration and invasion. Notably, RASA3 CanT and SomT transfections did not alter SNU1967, GES1 or AGS cellular proliferation rates (FIG. 13). To confirm that these observations are not due to non-physiological in vitro expression levels, we then examined NCC24 GC cells, which normally express high endogenous levels of RASA3 SomT and minimal RASA3 CanT (FIG. 13). Silencing of endogenous RASA3 SomT using two independent siRNA constructs significantly inhibited NCC24 migration and invasion (P<0.01-0.001) (FIG. 13), consistent with RASA3 SomT playing a role in promoting cancer migration and invasion.

In an earlier study, we reported a transcript isoform of the MET receptor tyrosine kinase, driven by an internal alternative promoter, which has been independently confirmed in other cancer types. However, functional implications of this MET variant remain unclear. RNA-seq and 5′ RACE analysis confirmed transcript expression of this shorter isoform, predicted to harbor a truncated SEMA domain (FIG. 14). To assess functional differences between wild type (WT) and variant (Var) MET, we performed transient transfections of MET(WT) and MET(Var) into HEK293 cells. In both untreated and HGF-treated conditions, MET-Var transfected cells exhibited significantly higher levels of p-Gab1 (Y627), a key mediator of MET signaling (e.g. 2.48-3.95 fold comparing MET-Var vs MET-WT, P=0.003 (untreated), P<0.05 (T15 and T30). (66) In addition, in HGF-untreated samples, cells transfected with MET-Var also exhibited higher p-ERK1/2 levels (2.74 fold) and also higher p-STAT3 (Y705)(67-70) levels (1.80 fold) compared to MET-WT (P=0.023 and P=0.026 for p-ERK and p-STAT3 (Y705) respectively). These results suggest that expression of the MET Var isoform may promote MET-downstream signaling kinetics in a manner important for GC tumorigenesis.

Somatic Promoters Correlate with Tumor Immunity

Cancer immunoediting is a process where developing tumors sculpt their immunogenic and antigenic profile to evade host immune surveillance. Mechanisms of cancer immunoediting are diverse, including upregulation of immune checkpoint inhibitors such as PD-L1. To explore potential contributions of somatic promoters to tumor immunity, we identified somatic promoter-associated N-terminal peptides with high predicted affinity binding to GC specific MHC Class I HLA alleles (Table 8 and 9), which are required for antigen presentation to CD8+ cytotoxic T cells (IC50≤50 nM, FIG. 4a ). Analysis of recurrent somatic promoter-associated peptides using the NetMHCpan-2.8 algorithm revealed a significant enrichment in high-affinity MHC I binding compared to multiple control peptide populations, including canonical GC peptides (average 36% vs 24%; P<0.01), randomly selected peptides (P<0.001), and C-terminal peptides (P<0.01) (FIG. 4B shows HLA-A, B, and C combined, FIG. 15A depicts data for HLA-A only). The majority of high affinity somatic promoter-associated peptides corresponded to situations where the somatic transcript lacking the N-terminal peptide is overexpressed in tumors relative to normal tissues (78% lost; 76/97 high-affinity peptides, FIG. 4C). Notably, because transcripts driven by the N-terminal lacking somatic TSSs are also overexpressed in tumors to a significantly greater degree than transcripts driven by the canonical TSS (P<0.05, Wilcoxon one sided test) (FIG. 12), such a scenario would be predicted to result in relative depletion of these N-terminal immunogenic peptides in tumors. Interestingly, an analogous N-terminal analysis using RNA-seq data alone (in the absence of epigenomic data) revealed that epigenome-guided N-terminal peptides exhibited significantly higher predicted immunogenicity scores compared to RNA-seq-only identified peptides (36.10% vs 27% for MHC presentation, P=0.02, Fisher Test), suggesting that epigenome-guided promoter identification can provide complementary value to RNA-seq-only guided analyses (FIG. 15).

TABLE 8 HLA prediction of GC samples Sample A1 A2 B1 B2 C1 C 2000639 A*33:03 A*24:02 B*58:01 B*40:01 C*03:02 C*03:67 2000721 A*11:01 A*11:01 B*46:01 B*15:01 C*01:02 C*04:01 2000986 A*24:02 A*11:01 B*40:01 B*38:02 C*07:02 C*15:02 980437 A*33:03 A*02:07 B*40:01 B*39:01 C*07:02 C*04:01 990068 A*02:03 A*11:01 B*51:01 B*55:02 C*08:01 C*14:02 2000085 A*24:07 A*34:01 B*15:21 B*15:21 C*04:03 C*04:03 980401 A*33:03 A*11:01 B*58:01 B*40:01 C*03:02 C*07:02 980447 A*11:01 A*11:01 B*38:02 B*27:04 C*12:02 C*07:02 2001206 A*02:07 A*24:02 B*46:01 B*40:06 C*01:02 C*08:01 980436 A*02:03 A*02:07 B*46:01 B*46:01 C*01:02 C*01:02 980417 A*33:03 A*11:01 B*58:01 B*46:01 C*03:02 C*01:02 980319 A*33:03 A*11:02 B*58:01 B*27:04 C*03:02 C*12:02 20021007 A*24:10 A*24:02 B*15:27 B*40:01 C*03:04 C*04:01

TABLE 9 Recurrent N terminal sequences with high affinity to MHC Class I SEQ ID NO. Gene N terminal sequence High Affinity HLA SEQ ID NO: 1847 ENSG00000007171.12 MACPWKFLFKTKFHQYA A*02:03, A*02:07, A*11:01,  MNGEKDINNNVEKAPCAT A*11:02, A*24:10, A*34:01,  SSPVTQDDLQYHNLSKQQ B*15:01, B*15:21, B*15:27,  NESPQPLVETGKKSPESLVK B*27:04, B*39:01, B*40:01,  LDATPLSSPRHVRIKNWGS B*46:01, B*58:01, C*03:02,  GMTFQDTLHHKAKGILTCR C*12:02 SKSCLGSIMTPKSLTRGPRD KPTPPDELLPQAIEFVNQYY GSFKEAKIEEHLARVEAVTK EIETTGTYQLTGDELIFATK QAWRNAPRCIGRIQWSNL QVFDARSCSTARE SEQ ID NO: 1848 ENSG00000011028.9 MGPGRPAPAPWPRHLLRC A*02:03, A*11:01, A*11:02,  VLLLGCLHLGRPGAPGDAA A*24:02, A*24:07, A*24:10,  LPEPNVFLIFSHGLQGCLEA A*33:03, B*15:01, B*15:27,  QGGQVRVTPACNTSLPAQ B*38:02, B*39:01, B*40:01,  RWKWVSRNRLFNLGTMQ B*40:06, B*51:01, B*58:01,  CLGTGWPGTNTTASLGMY C*03:02, C*03:04, C*12:02,  ECDREALNLRWHCRTLGD C*14:02 QLSLLLGARTSNISKPGTLE RGDQTRSGQWRIYGSEED LCALPYHEVYTIQGNSHGK PCTIPFKYDNQWFHGCTST GREDGHLWCATTQDYGK DERWGFCPIKSNDCETFW DKDQLTDSCYQFNFQSTLS WREAWASCEQQGADLLSI TEIHEQTYINGLLTGYSSTL WIGLNDLDTSGGWQWSD NSPLKYLNWESDQPDNPS EENCGVIRTESSGGWQNR DCSIALPYVCKKKPNATAEP TPPDRWANVKVECEPSW QPFQGHCYRLQAEKRSW QESKKACLRGGGDLVSIHS MAELEFITKQIKQEVEELWI GLNDLKLQMNFEWSDGSL VSFTHWHPFEPNNFRDSLE DCVTIWGPEGRWNDSPC NQSLPSICKKAGQLSQGAA EEDHGCRKGWTWHSPSC YWLGEDQVTYSEARRLCT DHGSQLVTITNREEQAFVS SLIYNWEGEYFWTALQDL NSTGSFFWLSGDEVMYTH WNRDQPGYSRGGCVALA TGSAMGLWEVKNCTSFRA RYICRQSLGTPVTPELPGPD PTPSLTGSCPQGWASDTKL RYCYKVFSSERLQDKKSWV QAQGACQELGAQLLSLASY EEEHFVANMLNKIFGESEP EIHEQHWFWIGLNRRDPR GGQSWRWSDGVGFSYHN FDRSRHDDDDIRGCAVLDL ASLQWVAMQCDTQLDWI CKIPRGTDVREPDDSPQGR REWLRFQEAEYKFFEHHST WAQAQRICTWFQAELTSV HSQAELDFLSHNLQKFSRA QEQHWWIGLHTSESDGRF RWTDGSIINFISWAPGKPR PVGKDKKCVYMTASRED WGDQRCLTALPYICKRSNV TKETQPPDLPTTALGGCPS DWIQFLNKCFQVQGQEPQ SRVKWSEAQFSCEQQEAQ LVTITNPLEQAFITASLPNV TFDLWIGLHASQRDFQWV EQEPLMYANWAPGEPSG PSPAPSGNKPTSCAVVLHS PSAHFTGRWDDRSCTEET HGFICQKGTDPSLSPSPAAL PPAPGTELSYLNGTFRLLQK PLRWHDALLLCESRNASLA YVPDPYTQAFLTQAARGLR TPLWIGLAGEEGSRRYSW VSEEPLNYVGWQDGEPQ QPGGCTYVDVDGAWRTT SCDTKLQGAVCGVSSGPPP PRRISYHGSCPQGLADSA WIPEREHCYSFHMELLLGH KEARQRCQRAGGAVLSILD EMENVFVWEHLQSYEGQS RGAWLGMNFNPKGGTLV WQDNTAVNYSNWGPPGL GPSMLSHNSCYWIQSNSG LWRPGACTNITMGVVCKL PRAEQSSFSPSALPENPAAL VVVLMAVLLLLALLTAALIL YRRRQSIERGAFEGARYSR SSSSPTEATEKNILVSDME MNEQQE SEQ ID NO: 1849 ENSG00000020256.15 MNASSEGESFAGSVQIPG A*02:03, B*15:01, C*03:02,  GTTVLVELTPDIHICGICKQ C*03:04 QFNNLDAFVAHKQSGCQL TGTSAAAPSTVQFVSEETV PATQTQTTTRTITSETQTIT VSAPEFVFEHGYQTY SEQ ID NO: 1850 ENSG00000032389.8 MEDDAPVIYGLEFQARALT A*02:03, A*24:07, A*24:10,  PQTAETDAIRFLVGTQSLKY A*33:03, B*15:01, B*15:21,  DNQIHIIDFDDENNIINKNV B*15:27, B*38:02, B*39:01,  LLHQAGEIWHISASPADRG B*40:01, B*40:06, B*46:01,  VLTTCYNRRDIIESFGILPVA B*51:01, B*55:02, B*58:01,  QSPTIVFVNTLHQVFFRGQ C*01:02, C*03:02, C*03:04,  VAASDSKVLTCAAVWR C*03:67, C*04:01, C*08:01,  C*12:02, C*14:02, C*15:02 SEQ ID NO: 1851 ENSG00000037042.8 MLEAILGGGGLPVEGRGST A*02:03, A*11:01, A*11:02,  EFEAFRLILFGSEDSVLPSPL A*24:02, A*24:07, A*24:10,  LYKMAHMGSDGGVLPVH B*40:01, B*40:06, B*51:01,  YATILFSL C*01:02, C*04:03, C*08:01,  C*14:02 SEQ ID NO: 1852 ENSG00000053747.11 MAAAARPRGRALGPVLPP A*02:03, A*11:01, A*11:02,  TPLLLLVLRVLPACGATARD A*24:02, A*24:07, A*24:10,  PGAAAGLSLHPTYFNLAEA A*33:03, B*15:01, B*39:01,  ARIWATATCGERGPGEGR B*40:01, B*55:02, B*58:01,  PQPELYCKLVGGPTAPGSG C*03:02, C*03:04, C*03:67,  HTIQGQFCDYCNSEDPRKA C*07:02, C*12:02, C*14:02,  HPVTNAIDGSERWWQSPP C*15:02 LSSGTQYNRVNLTLDLGQL FHVAYILIKFANSPRPDLWV LERSVDFGSTYSPWQYFAH SKVDCLKEFGREANMAVT RDDDVLCVTEYSRIVPLEN GEVVVSLINGRPGAKNFTF SHTLREFTKATNIRLRFLRT NTLLGHLISKAQRDPTVTR RYYYSIKDISIGGQCVCNGH AEVCNINNPEKLFRCECQH HTCGETCDRCCTGYNQRR WRPAAWEQSHECEACNC HGHASNCYYDPDVERQQA SLNTQGIYAGGGVCINCQH NTAGVNCEQCAKGYYRPY GVPVDAPDGCIPCSCDPEH ADGCEQGSGRCHCKPNFH GDNCEKCAIGYYNFPFCLRI PIFPVSTPSSEDPVAGDIKG CDCNLEGVLPEICDAHGRC LCRPGVEGPRCDTCRSGFY SFPICQACWCSALGSYQM PCSSVTGQCECRPGVTGQ RCDRCLSGAYDFPHCQGSS SACDPAGTINSNLGYCQCK LHVEGPTCSRCKLLYWNLD KENPSGCSECKCHKAGTVS GTGECRQGDGDCHCKSHV GGDSCDTCEDGYFALEKSN YFGCQGCQCDIGGALSSM CSGPSGVCQCREHVVGKV CQRPENNYYFPDLHHMKY EIEDGSTPNGRDLRFGFDP LAFPEFSWRGYAQMTSVQ NDVRITLNVGKSSGSLFRVI LRYVNPGTEAVSGHITIYPS WGAAQSKEIIFLPSKEPAFV TVPGNGFADPFSITPGIWV ACIKAEGVLLDYLVLLPRDY YEASVLQLPVTEPCAYAGP PQENCLLYQHLPVTRFPCT LACEARHFLLDGEPRPVAV RQPTPAHPVMVDLSGREV ELHLRLRIPQVGHYVVVVE YSTEAAQLFVVDVNVKSSG SVLAGQVNIYSCNYSVLCR SAVIDHMSRIAMYELLADA DIQLKGHMARFLLHQVCII PIEEFSAEYVRPQVHCIASY GRFVNQSATCVSLAHETPP TALILDVLSGRPFPHLPQQS SPSVDVLPGVTLKAPQNQ VTLRGRVPHLGRYVFVIHF YQAAHPTFPAQVSVDGG WPRAGSFHASFCPHVLGC RDQVIAEGQIEFDISEPEVA ATVKVPEGKSLVLVRVLVV PAENYDYQILHKKSMDKSL EFITNCGKNSFYLDPQTASR FCKNSARSLVAFYHKGALP CECHPTGATGPHCSPEGG QCPCQPNVIGRQCTRCAT GHYGFPRCKPCSCGRRLCE EMTGQCRCPPRTVRPQCE VCETHSFSFHPMAGCEGC NCSRRGTIEAAMPECDRDS GQCRCKPRITGRQCDRCAS GFYRFPECVPCNCNRDGTE PGVCDPGTGACLCKENVE GTECNVCREGSFHLDPANL KGCTSCFCFGVNNQCHSS HKRRTKFVDMLGWHLETA DRVDIPVSFNPGSNSMVA DLQELPATIHSASWVAPTS YLGDKVSSYGGYLTYQAKS FGLPGDMVLLEKKPDVQLT GQHMSIIYEETNTPRPDRL HHGRVHVVEGNFRHASSR APVSREELMTVLSRLADVRI QGLYFTETQRLTLSEVGLEE ASDTGSGRIALAVEICACPP AYAGDSC SEQ ID NO: 1853 ENSG00000059145.14 MPSVSKAAAAALSGSPPQ A*02:03, A*24:10, A*33:03,  TEKPTHYRYLKEFRTEQCPL B*15:01, B*39:01, B*40:01,  FSQHKCAQHRPFTCFHWH B*58:01, C*03:02, C*03:04,  FLNQRRRRPLRRRDGTFNY C*15:02 SPDVYCSKYNEATGVCPDG DECPYLHRTTGDTERKYHL RYYKTGTCIHETDARGHCV KNGLHCAFAHGPLDLRPPV CDVRELQAQEALQNGQLG GGEGVPDLQPGVLASQA MIEKILSEDPRWQDANFVL GSYKTEQCPKPPRLCRQGY ACPHYHNSRDRRRNPRRF QYRSTPCPSVKHGDEWGE PSRCDGGDGCQYCHSRTE QQFHPESTKCNDMRQTGY CPRGPFCAFAHVEKSLGM VNEWGCHDLHLTSPSSTG SGQPGNAKRRDSPAEGGP RGSEQDSKQNHLAVFAAV HPPAPSVSSSVASSLASSAG SGSSSPTALPAPPARALPLG PASSTVEAVLGSALDLHLS NVNIASLEKDLEEQDGHDL GAAGPRSLAGSAPVAIPGS LPRAPSLHSPSSASTSPLGS LSQPLPGPVGSSA SEQ ID NO: 1854 ENSG00000060656.15 MARAQALVLALTFQLCAPE A*02:03, A*11:01, A*11:02,  TETPAAGCTFEEASDPAVP A*24:02, A*24:10, A*33:03,  CEYSQAQYDDFQWEQVRI A*34:01, B*15:01, B*15:27,  HPGTRAPADLPHGSYLMV B*38:02, B*39:01, B*40:01,  NTSQHAPGQRAHVIFQSLS B*55:02, B*58:01, C*03:02,  ENDTHCVQFSYFLYSRDGH C*03:04, C*07:02, C*12:02,  SPGTLGVYVRVNGGPLGS C*14:02, C*15:02 AVWNMTGSHGRQWHQA ELAVSTFWPNEYQVLFEALI SPDRRGYMGLDDILLLSYP CAKAPHFSRLGDVEVNAG QNASFQCMAAGRAAEAE RFLLQRQSGALVPAAGVR HISHRRFLATEPLAAVSRAE QDLYRCVSQAPRGAGVSN FAELIVKEPPTPIAPPQLLRA GPTYLIIQLNTNSIIGDGPIV RKEIEYRMARGPWAEVHA VSLQTYKLWHLDPDTEYEI SVLLTRPGDGGTGRPGPPL ISRTKCAEPMRAPKGLAFA EIQARQLTLQWEPLGYNVT RCHTYTVSLCYHYTLGSSH NQTIRECVKTEQGVSRYTIK NLLPYRNVHVRLVLTNPEG RKEGKEVTFQTDEDVPSGI AAESLTFTPLEDMIFLKWEE PQEPNGLITQYEISYQSIESS DPAVNVPGPRRTISKLRNE TYHVFSNLHPGTTYLFSVR ARTGKGFGQAALTEITTNIS APSEDYADMPSPLGESENT ITVLLRPAQGRGAPISVYQV IVEEERARRLRREPGGQDC FPVPLTFEAALARGLVHYF GAELAASSLPEAMPFTVGD NQTYRGFWNPPLEPRKAY LIYFQAASHLKGETRLNCIRI ARKAACKESKRPLEVSQRS EEMGLILGICAGGLAVLILLL GAIIVIIRKGKPVNMTKATV NYRQEKTHMMSAVDRSFT DQSTLQEDERLGLSFMDT HGYSTRGDQRSGGVTEAS SLLGGSPRRPCGRKGSPYH TGQLHPAVRVADLLQHIN QMKTAEGYGFKQEYESFFE GWDATKKKDKVKGSRQEP MPAYDRHRVKLHPMLGD PNADYINANYIDGYHRSNH FIATQGPKPEMVYDFWR MVWQEHCSSIVMITKLVE VGRVKCSRYWPEDSDTYG DIKIMLVKTETLAEYVVRTF ALERRGYSARHEVRQFHFT AWPEHGVPYHATGLLAFIR RVKASTPPDAGPIVIHCSA GTGRTGCYIVLDVMLDMA ECEGVVDIYNCVKTLCSRR VNMIQTEEQYIFIHDAILEA CLCGETTIPVSEFKATYKEM IRIDPQSNSSQLREEFQTLN SVTPPLDVEECSIALLPRNR DKNRSMDVLPPDRCLPFLI STDGDSNNYINAALTDSYT RSAAFIVTLHPLQSTTPDF WRLVYDYGCTSIVMLNQL NQSNSAWPCLQYWPEPG RQQYGLMEVEFMSGTAD EDLVARVFRVQNISRLQEG HLLVRHFQFLRWSAYRDTP DSKKAFLHLLAEVDKWQA ESGDGRTIVHCLNGGGRS GTFCACATVLEMIRCHNLV DVFFAAKTLRNYKPNMVE TMDQYHFCYDVALEYLEGL ESR SEQ ID NO: 1855 ENSG00000066248.10 METRESEDLEKTRRKSASD A*02:03, A*11:01, A*11:01,  QWNTDNEPAKVKPELLPE A*11:02, A*11:02, A*24:02,  KEETSQADQDIQDKEPHC A*24:10, A*33:03, A*33:03,  HIPIKRNSIFNRSIRRKSKAK A*34:01, B*15:01, B*15:21,  ARDNPERNASCLADSQDN B*15:27, B*39:01, B*40:01,  GKSVNEPLTLNIPWSRMPP B*46:01, B*58:01, C*03:02,  CRT C*03:04, C*03:67, C*12:02,  C*14:02 SEQ ID NO: 1856 ENSG00000077092.14 MTTSGHACPVPAVNGHM A*24:02, A*24:07, A*24:10,  THYPATPYPLLFPPVIGGLS A*34:01, B*15:01, B*15:21,  LPPLHGLHGHPPPSGCSTP B*15:27, B*46:01, B*51:01,  SPATIETQS B*55:02, C*01:02, C*03:02,  C*04:01, C*07:02, C*12:02,  C*14:02 SEQ ID NO: 1857 ENSG00000079308.12 MTRLSWCFSCVIRWGKYL A*02:03, A*02:07, B*27:04,  FSCLLPLRFCLRSQPEDLEA B*39:01, B*46:01, C*01:02,  PKTHRFKVKTFKKVKPCGIC C*03:02, C*03:04, C*03:67,  RQVITQEGCTCKVCSFSCH C*08:01, C*14:02 RKCQAKVAAPCVPPSNHE LVPITTENAPKNVVDKGEG ASRGGNTRKSLEDNGSTRV TPSVQPHLQPIRN SEQ ID NO: 1858 ENSG00000080823.17 MKNYKAIGKIGEGTFSEVM A*02:03, A*33:03, B*40:01,  KMQSLRDGNYYACKQMK C*03:02, C*14:02 QRFESIEQVNNLREIQALRR LNPHPNILMLHEVVFDRKS GSLALICELMDMNIYELIRG RRYPLSEKKIMHYMYQLCK SLDHIHRNGIFHRDVKPENI LIKQDVLKLGD SEQ ID NO: 1859 ENSG00000097021.15 MARPGLIHSAPGLPDTCAL A*02:03 LQPPAASAAAAPS SEQ ID NO: 1860 ENSG00000100441.5 MPTWGARPASPDRFAVSA A*02:03, A*02:07, A*11:01,  EAENKVREQQPHVERIFSV A*11:02, A*24:02, A*24:07,  GVSVLPKDCPDNPHIWLQ A*24:10, A*33:03, B*15:01,  LEGPKENASRAKEYLKGLCS B*15:21, B*15:27, B*40:01,  PELQDEIHYPPKLHCIFLGA B*40:06, B*55:02, B*58:01,  QGFFLDCLAWSTSAHLVPR C*03:02, C*03:04, C*03:67,  APGSLMISGLTEAFVMAQS C*04:01, C*04:03, C*07:02,  RVEELAERLSWDFTPGPSS C*08:01, C*14:02, C*15:02 GASQCTGVLRDFSALLQSP GDAHREALLQLPLAVQEEL LSLVQEASSGQGPGALAS WEGRSSALLGAQCQGVRA PPSDGRESLDTGSMGPGD CRGARGDTYAVEKEGGKQ GGPREMDWGWKELPGEE AWEREVALRPQSVGGGAR ESAPLKGKALGKEEIALGG GGFCVHREPPGAHGSCHR AAQSRGASLLQRLHNGNA SPPRVPSPPPAPEPPWHC GDRGDCGDRGDVGDRGD KQQGMARGRGPQWKRG ARGGNLVTGTQRFKEALQ DPFTLCLANVPGQPDLRHI VIDGSNVAMVHGLQHYFS SRGIAIAVQYFWDRGHRDI TVFVPQWRFSKDAKVRES HFLQKLYSLSLLSLTPSRVM DGKRISSYDDRFMVKLAEE TDGIIVSNDQFRDLAEESEK W SEQ ID NO: 1861 ENSG00000103056.7 MVLYTTPFPNSCLSALHCV A*02:03, A*02:07, A*11:01,  SWALIFPCYWLVDRLAASF A*11:02, A*24:02, A*24:07,  IPTTYEKRQRADDPCCLQLL A*24:10, B*15:01, B*15:21,  CTALFTPIYLALLVASLPFAF B*15:27, B*27:04, B*38:02,  LGFLFWSPLQSARRPYIYSR B*39:01, B*40:01, B*40:06,  LEDKGLAGGAALLSEWKG B*46:01, B*51:01, B*55:02,  TGPGKSFCFATANVCLLPD B*58:01, C*01:02, C*03:02,  SLARVNNLFNTQARAKEIG C*03:04, C*03:67, C*04:01,  QRIRNGAARPQIKIYIDSPT C*04:03, C*07:02, C*08:01,  NTSISAASFSSLVSPQGGD C*12:02, C*15:02 GVARAVPGSIKRTASVEYK GDGGRHPGDEAANGPAS GDPVDSSSPEDACIVRIGG EEGGRPPEADDPVPGGQA RNGAGGGPRGQTPNHNQ QDGDSGSLGSPSASRESLV KGRAGPDTSASGEPGANS KLLYKASVVKKAAARRRRH PDEAFDHEVSAFFPANLDF LCLQEVFDKRAATKLKEQL HGYFEYILYDVGVYGCQGC CSFKCLNSGLLFASRYPI SEQ ID NO: 1862 ENSG00000103227.14 MLGAGLIKIRGDRCWRDL A*02:03, A*11:01, A*11:02,  TCMDFHYETQPMPNPVA A*24:02, A*24:07, A*24:10,  YYLHHSPWWFHRFETLSN A*33:03, B*15:01, B*38:02,  HFIELLVPFFLFLGRRACIIH B*40:01, B*58:01, C*03:02,  GVLQILFQAVLIVSGNLSFL C*03:04, C*07:02, C*14:02,  NWLTMVPSLACFDDATLG C*15:02 FLFPSGPGSLKDRVLQMQ RDIRGARPEPRFGSVVRRA ANVSLGVLLAWLSVPVVLN LLSSRQVMNTHFNSLHIVN TYGAFGSITKERAEVILQGT ASSNASAPDAMWEDYEFK CKPGDPSRRPCLISPYHYRL DWLMWFAAFQTYEHND WIIHLAGKLLASDAEALSLL AHNPFAGRPPPRWVRGE HYRYKFSRPGGRHAAEGK WWVRKRIGAYFPPLS SEQ ID NO: 1863 ENSG00000105559.7 MEGSRPRSSLSLASSASTIS A*02:03, A*11:01, A*11:02,  SLSSLSPKKPTRAVNKIHAF A*24:10, A*33:03, B*39:01,  GKRGNALRRDPNLPVHIR B*40:01, B*58:01, C*03:02,  GWLHKQDSSGLRLWKRR C*03:04, C*14:02 WFVLSGHCLFYYKDSREES VLGSVLLPSYNIRPDGPGA PRGRRFTFTAEHPGMRTY VLAADTLEDLRGWLRALG RASRAEGDDYGQPRSPAR PQPGEGPGGPGGPPEVSR GEEGRISESPEVTRLSRGRG RPRLLTPSPTTDLHSGLQM RRARSPDLFTPLSRPPSPLS LPRPRSAPARRPPAPSGDT APPARPHTPLSRIDVRPPLD WGPQRQTLSRPPTPRRGP PSEAGGGKPPRSPQHWSQ EPRTQAHSGSPTYLQLPPR PPGTRASMVLLPGPPLEST FHQSLETDTLLTKLCGQDR LLRRLQEEIDQKQEEKEQLE AALELTRQQLGQATREAG APGRAWGRQRLLQDRLVS VRATLCHLTQERERVWDT YSGLEQELGTLRETLEYLLH LGSPQDRVSAQQQLWMV EDTLAGLGGPQKPPPHTEP DSPSPVLQGEESSERESLPE SLELSSPRSPETDWGRPPG GDKDLASPHLGLGSPRVSR ASSPEGRHLPSPQLGTKAP VARPRMSAQEQLERMRR NQECGRPFPRPTSPRLLTL GRTLSPARRQPDVEQRPV VGHSGAQKWLRSSGSWSS PRNTTPYLPTSEGHRERVLS LSQALATEASQWHRMMT GGNLDSQGDPLPGVPLPP SDPTRQETPPPRSPPVANS GSTGFSRRGSGRGGGPTP WGPAWDAGIAPPVLPQD EGAWPLRVTLLQSSF SEQ ID NO: 1864 ENSG00000105639.14 MAPPSEETPLIPQRSCSLLS A*02:03, A*11:01, A*11:02,  TEAGALHVLLPARGPGPPQ A*24:02, A*24:07, A*24:10,  RLSFSFGDHLAEDLCVQAA A*33:03, B*15:01, B*39:01,  KASGILPVYHSLFALATEDL B*40:01, B*55:02, B*58:01,  SCWFPPSHIFSVEDASTQV C*03:02, C*03:04, C*07:02,  LLYRIRFYFPNWFGLEKCHR C*14:02 FGLRKDLASAILDLPVLEHL FAQHRSDLVSGRLPVGLSL KEQGECLSLAVLDLARMAR EQAQRPGELLKTVSYKACL PPSLRDLIQGLSFVTRRRIR RTVRRALRRVAACQADRH SLMAKYIMDLERLDPAGA AETFHVGLPGALGGHDGL GLLRVAGDGGIAWTQGEQ EVLQPFCDFPEIVDISIKQA PRVGPAGEHRLVTVTRTD NQILEAEFPGLPEALSFVAL VDGYFRLTTDSQHFFCKEV APPRLLEEVAEQCHGPITLD FAINKLKTGGSRPGSYVLRR SPQDFDSFLLTVCVQNPLG PDYKGCLIRRSPTGTFLLVG LSRPHSSLRELLATCWDGG LHVDGVAVTLTSCCIPRPKE KSNLIVVQRGHSPPTSSLV QPQSQYQLSQMTFHKIPA DSLEWHENLGHGSFTKIYR GCRHEVVDGEARKTEVLLK VMDAKHKNCMESFLEAAS LMSQVSYRHLVLLHGVCM AGDSTMVQEFVHLGAIDM YLRKRGHLVPASWKLQVV KQLAYALNYLEDKGLPHGN VSARKVLLAREGADGSPPFI KLSDPGVSPAVLSLEMLTD RIPWVAPECLREAQTLSLE ADKWGFGATVWEVFSGV TMPISALDPAKKLQFYEDR QQLPAPKWTELALLIQQC MAYEPVQRPSFRAVIRDLN SLISSDYELLSDPTPGALAPR DGLWNGAQLYACQDPTIF EERHLKYISQLGKGNFGSV ELCRYDPLGDNTGALVAVK QLQHSGPDQQRDFQREIQ ILKALHSDFIVKYRGVSYGP GRQSLRLVMEYLPSGCLRD FLQRHRARLDASRLLLYSSQ ICKGMEYLGSRRCVHRDLA ARNILVESEAHVKIADFGLA KLLPLDKDYYVVREPGQSPI FWYAPESLSDNIFSRQSDV WSFGVVLYELFTYCDKSCS PSAEFLRMMGCERDVPAL CRLLELLEEGQRLPAPPACP AEVHELMKLCWAPSPQDR PSFSALGPQLDMLWSGSR GCETHAFTAHPEGKHHSLS FS SEQ ID NO: 1865 ENSG00000105650.17 MQAPVPHSQRRESFLYRS A*02:03, B*15:01, B*39:01,  DSDYELSPKAMSRNSSVAS B*40:01, C*03:02, C*03:04,  DLHGEDMIVTPFAQVLASL C*15:02 RTVRSNVAALARQQCLGA AKQGPVGN SEQ ID NO: 1866 ENSG00000105963.9 MAKERRRAVLELLQRPGN A*02:03, A*24:10, B*15:01,  ARCADCGAPDPDWASYTL C*03:02, C*03:04 GVFICLSCSGIHRNIPQVSK VKSVRLDAWEEAQVEFMA SHGNDAARARFESKVPSFY YRPTP SEQ ID NO: 1867 ENSG00000105976.10 MKAPAVLAPGILVLLFTLV A*02:03, A*11:01, A*11:02,  QRSNGECKEALAKSEMNV A*24:02, A*24:07, A*24:10,  NMKYQLPNFTAETPIQNVI A*33:03, A*34:01, B*15:01,  LHEHHIFLGATNYIYVLNEE B*15:27, B*39:01, B*40:01,  DLQKVAEYKTGPVLEHPDC B*58:01, C*03:02, C*03:04,  FPCQDCSSKANLSGGVWK C*03:67, C*07:02, C*12:02,  DNINMALVVDTYYDDQLIS C*14:02, C*15:02 CGSVNRGTCQRHVFPHNH TADIQSEVHCIFSPQIEEPS QCPDCVVSALGAKVLSSVK DRFINFFVGNTINSSYFPDH PLHSISVRRLKETKDGFMFL TDQSYIDVLPEFRDSYPIKY VHAFESNNFIYFLTVQRETL DAQTFHTRIIRFCSINSGLH SYMEMPLECILTEKRKKRST KKEVFNILQAAYVSKPGAQ LARQIGASLNDDILFGVFA QSKPDSAEPMDRSAMCAF PIKYVNDFFNKIVNKNNVR CLQHFYGPNHEHCFNRTLL RNSSGCEARRDEYRTEFTT ALQRVDLFMGQFSEVLLTS ISTFIKGDLTIANLGTSEGRF MQVVVSRSGPSTPHVNFL LDSHPVSPEVIVEHTLNQN GYTLVITGKKITKIPLNGLGC RHFQSCSQCLSAPPFVQCG WCHDKCVRSEECLSGTWT QQICLPAIYKVFPNSAPLEG GTRLTICGWDFGFRRNNK FDLKKTRVLLGNESCTLTLS ESTMNTLKCTVGPAMNKH FNMSIIISNGHGTTQYSTFS YVDPVITSISPKYGPMAGG TLLTLTGNYLNSGNSRHISI GGKTCTLKSVSNSILECYTP AQTISTEFAVKLKIDLANRE TSIFSYREDPIVYEIHPTKSFI SGGSTITGVGKNLNSVSVP RMVINVHEAGRNFTVACQ HRSNSEIICCTTPSLQQLNL QLPLKTKAFFMLDGILSKYF DLIYVHNPVFKPFEKPVMIS MGNENVLEIKGNDIDPEA VKGEVLKVGNKSCENIHLH SEAVLCTVPNDLLKLNSELN IEWKQAISSTVLGKVIVQP DQNFTGLIAGVVSISTALLL LLGFFLWLKKRKQIKDLGSE LVRYDARVHTPHLDRLVSA RSVSPTTEMVSNESVDYRA TFPEDQFPNSSQNGSCRQ VQYPLTDMSPILTSGDSDIS SPLLQNTVHIDLSALNPELV QAVQHVVIGPSSLIVHFNE VIGRGHFGCVYHGTLLDN DGKKIHCAVKSLNRITDIGE VSQFLTEGIIMKDFSHPNVL SLLGICLRSEGSPLVVLPYM KHGDLRNFIRNETHNPTVK DLIGFGLQVAKGMKYLASK KFVHRDLAARNCMLDEKF TVKVADFGLARDMYDKEY YSVHNKTGAKLPVKWMAL ESLQTQKFTTKSDVWSFGV LLWELMTRGAPPYPDVNT FDITVYLLQGRRLLQPEYCP DPLYEVMLKCWHPKAEM RPSFSELVSRISAIFSTFIGEH YVHVNATYVNVKCVAPYP SLLSSEDNADDEVDTRPAS FWETS SEQ ID NO: 1868 ENSG00000107317.7 MATHHTLWMGLALLGVL A*02:03, B*15:01, C*03:02,  GDLQAAPEAQVSVQPNFQ C*03:04, C*12:02 QD SEQ ID NO: 1869 ENSG00000111700.8 MDQHQHLNKTAESASSEK A*11:01, A*11:02 KKTRRCNGFK SEQ ID NO: 1870 ENSG00000111860.9 MWGRFLAPEASGRDSPG A*02:03, A*11:01, A*11:02,  GARSFPAGPDYSSAWLPA A*24:02, A*24:07, A*24:10,  NESLWQATTVPSNHRNN A*33:03, B*15:01, B*15:27,  HIRRHSIASDSGDTGIGTSC B*39:01, B*40:01, C*03:02,  SDSVEDHSTSSGTLSFKPSQ C*03:04, C*14:02 SLITLPTAHVMPSNSSASIS KLRESLTPDGSKWSTSLMQ TLGNHSRGEQDSSLDMKD FRPLRKWSSLSKLTAPDNC GQGGTVCREESRNGLEKIG KAKALTSQLRTIGPSCLHDS MEMLRLEDKEINKKRSSTL DCKYKFESCSKEDFRASSST LRRQPVDMTYSALPESKPI MTSSEAFEPPKYLMLGQQ AVGGVPIQPSVRTQMWLT EQLRTNPLEGRNTEDSYSL APWQQQQIEDFRQGSETP MQVLTGSSRQSYSPGYQD FSKWESMLKIKEGLLRQKEI VIDRQKQQITHLHERIRDN ELRAQHAMLGHYVNCEDS YVASLQPQYENTSLQTPFS EESVSHSQQGEFEQKLAST EKEVLQLNEFLKQRLSLFSE EKKKLEEKLKTRDRYISSLKK KCQKESEQNKEKQRRIETL EKYLADLPTLDDVQSQSLQ LQILEEKNKNLQEALIDTEK KLEEIKKQCQDKETQLICQK KKEKELVTTVQSLQQKVER CLEDGIRLPMLDAKQLQNE NDNLRQQNETASKIIDSQQ DEIDRMILEIQSMQGKLSK EKLTTQKMMEELEKKERN VQRLTKALLENQRQTDETC SLLDQGQEPDQSRQQTVL SKRPLFDLTVIDQLFKEMSC CLFDLKALCSILNQRAQGK EPNLSLLLGIRSMNCSAEET ENDHSTETLTKKLSDVCQL RRDIDELRTTISDRYAQDM GDNCITQ SEQ ID NO: 1871 ENSG00000111912.14 XEKTCSSLEREPHFSLLTMR A*02:03, A*11:01, A*11:02,  GQRLPLDIQIFYCARPDEEP A*24:02, A*24:07, A*24:10,  FVKIITVEEAKRRKSTCSYYE A*33:03, B*15:01, B*15:27,  DEDEEVLPVLRPHSALLEN B*40:01, B*55:02, C*03:02,  MHIEQLARRLPARVQGYP C*03:04, C*03:67, C*12:02,  WRLAYSTLEHGTSLKTLYRK C*14:02, C*15:02 SASLDSPVLLVIKDMDNQIF GAYATHPFKFSDHYYGTGE TFLYTFSPHFKVFKWSGEN SYFINGDISSLELGGGGGRF GLWLDADLYHGRSNSCST FNNDILSKKEDFIVQDLEV WAFD SEQ ID NO: 1872 ENSG00000112033.9 MEQPQEEAPEVREEEEKEE A*02:03, A*02:07, A*11:01,  VAEAEGAPELNGGPQHAL A*11:02, A*24:02, A*24:07,  PSSSYTDLSRSSSPPSLLDQL A*24:10, A*33:03, A*34:01,  QMGCDGASCGSLNMECR B*15:01, B*15:21, B*15:27,  VCGDKASGFHYGVHACEG B*27:04, B*38:02, B*39:01,  CKGFFRRTIRMKLEYEKCER B*40:01, B*40:06, B*46:01,  SCKIQKKNRNKCQYCRFQK B*51:01, B*55:02, B*58:01,  CLALGMSHNAIRFGRMPE C*01:02, C*03:02, C*03:04,  AEKRKLVAGLTANEGSQYN C*04:01, C*04:03, C*07:02,  PQVADLKAFSKHIYNAYLK C*08:01, C*12:02, C*15:02 NFNMTKKKARSILTGKASH TAPFVIHDIETLWQAEKGL VWKQLVNGLPPYKEISVHV FYRCQCTTVETVRELTEFAK SIPSFSSLFLNDQVTLLKYG VHEAIFAMLASIVNKDGLL VANGSGFVTREFLRSLRKP FSDIIEPKFEFAVKFNALELD DSDLALFIAAIILCGDRPGL MNVPRVEAIQDTILRALEF HLQANHPDAQYLFP SEQ ID NO: 1873 ENSG00000113594.5 MMDIYVCLKRPSWMVDN A*02:03, A*11:01, A*11:02,  KRMRTASNFQWLLSTFILL A*24:02, A*24:07, A*24:10,  YLMNQVNSQKKGAPHDLK A*33:03, A*34:01, B*15:01,  CVTNNLQVWNCSWKAPS B*39:01, B*40:01, B*58:01,  GTGRGTDYEVCIENRSRSC C*03:02, C*03:04, C*03:67,  YQLEKTSIKIPALSHGDYEITI C*12:02, C*14:02, C*15:02 NSLHDFGSSTSKFTLNEQN VSLIPDTPEILNLSADFSTST LYLKWNDRGSVFPHRSNVI WEIKVLRKESMELVKLVTH NTTLNGKDTLHHWSWAS DMPLECAIHFVEIRCYIDNL HFSGLEEWSDWSPVKNIS WIPDSQTKVFPQDKVILVG SDITFCCVSQEKVLSALIGH TNCPLIHLDGENVAIKIRNIS VSASSGTNVVFTTEDNIFG TVIFAGYPPDTPQQLNCET HDLKEIICSWNPGRVTALV GPRATSYTLVESFSGKYVRL KRAEAPTNESYQLLFQMLP NQEIYNFTLNAHNPLGRSQ STILVNITEKVYPHTPTSFKV KDINSTAVKLSWHLPGNFA KINFLCEIEIKKSNSVQEQR NVTIKGVENSSYLVALDKL NPYTLYTFRIRCSTETFWK WSKWSNKKQHLTTEASPS KGPDTWREWSSDGKNLIIY WKPLPINEANGKILSYNVS CSSDEETQSLSEIPDPQHKA EIRLDKNDYIISVVAKNSVG SSPPSKIASMEIPNDDLKIE QVVGMGKGILLTWHYDP NMTCDYVIKWCNSSRSEP CLMDWRKVPSNSTETVIES DEFRPGIRYNFFLYGCRNQ GYQLLRSMIGYIEELAPIVA PNFTVEDTSADSILVKWED IPVEELRGFLRGYLFYFGKG ERDTSKMRVLESGRSDIKV KNITDISQKTLRIADLQGKT SYHLVLRAYTDGGVGPEKS MYVVTKENSVGLIIAILIPVA VAVIVGVVTSILCYRKREWI KETFYPDIPNPENCKALQF QKSVCEGSSALKTLEMNPC TPNNVEVLETRSAFPKIEDT EIISPVAERPEDRSDAEPEN HVVVSYCPPIIEEEIPNPAA DEAGGTAQVIYIDVQSMY QPQAKPEEEQENDPVGGA GYKPQMHLPINSTVEDIAA EEDLDKTAGYRPQANVNT WNLVSPDSPRSIDSNSEIVS FGSPCSINSRQFLIPPKDED SPKSNGGGWSFTNFFQNK PND SEQ ID NO: 1874 ENSG00000114541.10 MASVFMCGVEDLLFSGSR A*02:03, A*11:01, A*11:02,  FVWNLTVSTLRRWYTERLR A*24:10, A*33:03, A*34:01,  ACHQVLRTWCGLQDVYQ B*40:01, B*58:01, C*07:02,  MTEGRHCQVHLLDDRRLE C*12:02, C*14:02 LLVQPKLLARELLDLVASHF NLKEKEYFGITFIDDTGQQ NWLQLDHRVLDHDLPKKP GPTILHFAVRFYIESISFLKD KTTVELFFLNAKACVHKGQ IEVESETIFKLAAFILQEAKG DYTSDENARKDLKTLPAFP TKTLQEHPSLAYCEDRVIEH YLKIKGLTRGQAVVQY SEQ ID NO: 1875 ENSG00000115977.14 MKKFFDSRREQGGSGLGS A*02:03, A*11:01, A*11:02,  GSSGGGGSTSGLGSGYIGR A*24:02, A*24:07, A*24:10,  VFGIGRQQVTVDEVLAEG B*15:01, B*39:01, B*40:01,  GFAIVFLVRTSNGMKCALK C*03:02, C*12:02, C*14:02 RMFVNNEHDLQVCKREIQI MRDLSGHKNIVGYIDSSIN NVSSGDVWEVLILMDFCR GGQVVNLMNQRLQTGFT ENEVLQIFCDTCEAVARLH QCKTPIIHRDLKVENILLHD RGHYVLCDFGSATNKFQN PQTEGVNAVEDEIKKYTTL SYRAPEMVNLYSGKIITTKA DIWALGCLLYKLCYFTLPFG ESQVAICDGNFTIPDNSRYS QDMHCLIRYMLEPDPDKR PDIYQVSYFSFKLLKKECPIP NVQNSPIPAKLPEPVKASE AAAKKTQPKARLTDPIPTTE TSIAPRQRPKAGQTQPNP GILPIQPALTPRKRATVQPP PQAAGSSNQPGLLASVPQ PKPQAPPSQPLPQTQAKQ PQAPPTPQQTPSTQAQGL PAQAQATPQHQQQLFLK QQQQQQQPPPAQQQPA GTFYQQQQAQTQQFQAV HPATQKPAIAQFPVVSQG GSQQQLMQNFYQQQQQ QQQQQQQQQLATALHQ QQLMTQQAALQQKPTMA AGQQPQPQPAAAPQPAP AQEPAIQAPVRQQPKVQT TPPPAVQGQKVGSLTPPSS PKTQRAGHRRILSDVTHSA VFGVPASKSTQLLQAAAAE AELLDPGRQTLQ SEQ ID NO: 1876 ENSG00000116833.9 MSSNSDTGDLQESLKHGLT A*02:03 PIGAGLPDRHGSPIPARGR LV SEQ ID NO: 1877 ENSG00000118855.14 MDAGKLARHPTDTGSERA C*03:02, C*03:04, C*14:02 VPALAEIRPWWAPPLRPQ SEQ ID NO: 1878 ENSG00000119547.5 MKAAYTAYRCLTKDLEGCA A*02:03, A*11:01, A*11:02,  MNPELTMESLGTLHGPAG A*24:10, A*33:03, B*15:01,  GGSGGGGGGGGGGGGG B*15:27, B*39:01, B*58:01,  GPGHEQELLASPSPHHAG C*03:02, C*03:04, C*07:02,  RGAAGSLRGPPPPPTAHQ C*14:02 ELGTAAAAAAAASRSAMV TSMASILDGGDYRPELSIPL HHAMSMSCDSSPPGMG MSNTYTTLTPLQPLPPISTV SDKFHHPHPHHHPHHHH HHHHQRLSGNVSGSFTLM RDERGLPAMNNLYSPYKE MPGMSQSLSPLAATPLGN GLGGLHNAQQSLPNYGPP GHDKMLSPNFDAHHTAM LTRGEQHLSRGLGTPPAA MMSHLNGLHHPGHTQSH GPVLAPSRERPPSSSSGSQ VATSGQLEEINTKEVAQRIT AELKRYSIPQAIFAQRVLCR SQGTLSDLLRNPKPWSKLK SGRETFRRMWKWLQEPEF QRMSALRLAA SEQ ID NO: 1879 ENSG00000125826.15 MDEKTKKAEEMALSLTRA A*02:03, A*02:07, A*11:01,  VAGGDEQVAMKCAIWLA A*11:02, A*24:10, A*33:03,  EQRVPLSVQLKPEVSPTQD B*40:01, C*03:02, C*03:04 IRLWVSVEDAQMHTVTIW LTVRPDMTVASLKDMVFL DYGFPPVLQQWVIGQRLA RDQETLHSHGVRQNGDSA YLYLLSARNTSLNPQELQRE RQLRMLEDLGFKDLTLQPR GPLEPGPPKPGVPQEPGR GQPDAVPEPPPVGWQCP GCTFINKPTRPGCEMCCRA RPEAYQVPASYQPDEEERA RLAGEEEALRQYQQRKQQ QQEGNYLQHVQLDQRSLV LNTEPAECPVCYSVLAPGE AVVLRECLHTFCRECLQGTI RNSQEAEVSCPFIDNTYSCS GKLLEREIKALLTPEDYQRF LDLGISIAENRSAFSYHCKT PDCKGWCFFEDDVNEFTC PVCFHVNCLLCKAIHEQM NCKEYQEDLALRAQNDVA ARQTTEMLKVMLQQGEA MRCPQCQIVVQKKDGCD WIRCTVCHTEICWVTKGPR WGPGGPGDTSGGCRCRV NGIPCHPSCQNCH SEQ ID NO: 1880 ENSG00000129116.13 MSALASRSAPAMQSSGSF A*02:03, A*11:01, A*11:02,  NYARPKQFIAAQNLGPAS A*24:02, A*24:10, A*33:03,  GHGTPASSPSSSSLPSPMS B*15:01, B*39:01, B*40:01,  PTPRQFGRAPVPPFAQPF B*58:01, C*03:02, C*03:04 GAEPEAPWGSSSPSPPPPP PPVFSPTAAFPVPDVFPLPP PPPPLPSPGQASHCSSPAT RFGHSQTPAAFLSALLPSQ PPPAAVNALGLPKGVTPA GFPKKASRTARIASDEEIQG TKDAVIQDLERKLRFKEDLL NNGQPRLTYEERMARRLL GADSATVFNIQEPEEETAN QEYKVSSCEQRLISEIEYRLE RSPVDESGDEVQYGDVPV ENGMAPFFEMKLKHYKIFE GMPVTFTCRVAGNPKPKIY WFKDGKQISPKSDHYTIQR DLDGTCSLHTTASTLDDDG NYTIMAANPQGRISCTGRL MVQAVNQRGRSPRSPSG HPHVRRPRSRSRDSGDEN EPIQERFFRPHFLQAPGDLT VQEGKLCRMDCKVSGLPT PDLSWQLDGKPVRPDSAH KMLVRENGVHSLIIEPVTSR DAGIYTCIATNRAGQNSFS LELVVAAKE SEQ ID NO: 1881 ENSG00000129682.9 MSGKVTKPKEEKDASKVLD A*02:03, A*02:07, A*24:10,  DAPPGTQEYIMLRQDSIQS A*34:01, B*27:04, B*38:02,  AELKKKESPFRAKCHEIFCC B*39:01, B*46:01, B*55:02,  PLKQVHHKENTEPEEPQLK C*03:02, C*07:02, C*08:01,  GIVTKLYSRQGYHLQLQAD C*15:02 GTIDGTKDEDSTYTLFNLIP VGLRVVAIQGVQTKLYLA SEQ ID NO: 1882 ENSG00000131374.10 MYHSLSETRHPLQPEEQEV A*02:03, A*24:02, A*24:07,  GIDPLSSYSNKSGGDSNKN A*24:10, A*33:03, B*27:04,  GRRTSSTLDSEGTFNSYRKE B*51:01, C*07:02, C*15:02 WEELFVNNNYLATIRQKGI NGQLRSSRFRSICWKLFLC VLPQDKSQWISRIEELRAW YSNIKEIHITNPRKVVGQQ DL SEQ ID NO: 1883 ENSG00000131620.13 MWEASGMEERALEELAM A*02:03, A*24:10, A*33:03,  EETALDPLLAEAAGAVDGE B*38:02, B*40:01, C*01:02 GAPPGGPSAQAATMRVN EKYSTLPAEDRSVHIINICAI EDIGYLPSEGTLLNSLSVDP DAECKYGLYFRDGRRKVDY ILVYHHKRPSGNRTLVRRV QHSDTPSGARSVKQDHPL PGKGASLDAGSGEPP SEQ ID NO: 1884 ENSG00000132005.4 MATQAYTELQAAPPPSQP B*15:01, B*58:01, C*03:02,  PQAPPQAQPQPPPPPPPA C*03:04, C*03:67, C*12:02,  APQPPQPPTAAATPQPQY C*14:02 VTELQSPQPQAQPPGGQK QYVTELPAVPAPSQPTGAP TPSPAPQQYIVVTVSEGAM RASETVSEASPGSTASQTG VPTQVVQQVQGTQQRLL VQTSVQAKPGHVSPLQLT NIQVPQQALPTQRLVVQS AAPGSKGGQVSLTVHGTQ QVHSPPEQSPVQANSSSSK TAGAPTGTVPQQLQVHGV QQSVPVTQERSVVQATPQ APKPGPVQPLTVQGLQPV HVAQEVQQLQQVPVPHV YSSQVQYVEGGDASYTASA IRSSTYSYPETPLYTQTASTS YYEAAGTATQVSTPATSQA VASSGS SEQ ID NO: 1885 ENSG00000132359.9 MFGRKRSVSFGGFGWIDK A*02:03, A*11:01, A*11:02,  TMLASLKVKKQELANSSDA A*34:01, B*40:01, C*03:02,  TLPDRPLSPPLTAPPTMKSS C*03:04, C*14:02, C*15:02 EFFEMLEKMQGIKLEEQKP GPQKNKDDYIPYPSIDEVV EKGGPYPQVILPQFGGYWI EDPENVGTPTSLGSSICEEE EEDNLSPNTFGYKLECKGE ARAYRRHFLGKDHLNFYCT GSSLGNLILSVKCEEAEGIEY LRVILRSKLKTVHERIPLAGL SKLPSVPQIAKAFCDDAVG LRFNPVLYPKASQ SEQ ID NO: 1886 ENSG00000134490.9 MCVRRSLVGLTFCTCYLAS A*02:03, A*11:01, A*11:02,  YLTNKYVLSVLKFTYPTLFQ A*24:02, A*24:07, A*24:10,  GWQTLIGGLLLHVSWKLG A*33:03, B*15:01, B*15:27,  WVEINSSSRSHVLVWLPAS B*58:01, C*03:02, C*03:04,  VLFVGIIYAGSRALSRLAIPV C*12:02 FLTLHNVAEVIICGYQKCFQ KEKTSPAKICSALLLLAAAG CLPFNDSQFNPDGYFWAII HLLCVGAYKILQKSQKPSAL SDIDQQYLNYIFSVVLLAFA SHPTGDLFSVLDFPFLYFYR FHGSCCASGFLGFFLMFST VKLKNLLAPGQCAAWIFFA KIITAGLSILLFDAILTSATTG CLLLGALGEALLVFSERKSS SEQ ID NO: 1887 ENSG00000135093.8 MLSSRAEAAMTAADRAIQ A*02:03, A*02:07, A*11:01,  RFLRTGAAVRYKVMKNW A*11:02, A*24:02, A*24:07,  GVIGGIAAALAAGIYVIWG A*24:10, B*15:21, B*27:04,  PITERKKRRKGLVPGLVNL B*38:02, B*39:01, B*40:01,  GNTCFMNSLLQGLSACPA B*51:01, B*58:01, C*03:02,  FIRWLEEFTSQYSRDQKEP C*07:02, C*14:02, C*15:02 PSHQYLSLTLLHLLKALSCQ EVTDDEVLDASCLLDVLRM YRWQISSFEEQDAHELFHV ITSSLEDERDRQPRVTHLFD VHSLEQQSEITPKQITCRTR GSPHPTSNHWKSQHPFHG RLTSN SEQ ID NO: 1888 ENSG00000136231.9 MNKLYIGNLSENAAPSDLE A*02:03, A*11:01, A*11:02,  SIFKDAKIPVSGPFLVKTGY A*24:10, A*33:03, A*34:01,  AFVDCPDESWALKAIEALS B*15:01, B*15:27, C*03:02,  GKIELHGKPIEVEHSVPKRQ C*03:04, C*14:02 RIRKLQIRNIPPHLQWEVLD SLLVQYGVVESCEQVNTDS ETAVVNVTYSSKDQARQA LDKLNGFQLENFTLKVAYIP DEMAAQQNPLQQPRGRR GLGQRGSSRQGSPGSVSK QKPCDLPLRLLVPTQFVGAI IGKEGATIRNITKQTQSKID VHRKENAGAAEKSITILSTP EGTSAACKSILEIMHKEAQ DIKFTEEIPLKILAHNNFVG RLIGKEGRNLKKIEQDTDTK ITISPLQELTLYNPERTITVK GNVETCAKAEEEIMKKIRE SYENDIASMNLQAHLIPGL NLNALGLFPPTSGMPPPTS GPPSAMTPPYPQFEQSETE TVHLFIPALSVGAIIGKQGQ HIKQLSRFAGASIKIAPAEA PDAKVRMVIITGPPEAQFK AQGRIYGKIKEENFVSPKEE VKLEAHIRVPSFAAGRVIGK GGKTVNELQNLSSAEVVVP RDQTPDENDQVVVKITGH FYACQVAQRKIQEILTQVK QHQQQKALQSGPPQSRRK SEQ ID NO: 1889 ENSG00000136848.12 MEPDSLLDQDDSYESPQE A*02:03 RPGSRRSLPGSLSEKSPSM EPSAATPFRVTGFLSRRLKG SIKRTKSQPKLDRNHSFRHI SEQ ID NO: 1890 ENSG00000137203.6 MLWKLTDNIKYEDCEDRH A*02:03, A*11:01, A*11:02,  DGTSNGTARLPQLGTVGQ A*24:02, A*24:10, A*33:03,  SPYTSAPPLSHTPNADFQP B*39:01, C*14:02 PYFPPPYQPIYPQSQDPYS HVNDPYSLNPLHAQPQPQ HPGWPGQRQSQESGLLHT HRGLPHQLSGLDPRRDYRR HEDLLHGPHALSSGLGDLSI HSLPHAIEEVPHVEDPGINI PDQTVIKKGPVSLSKSNSN AVSAIPINKDNLFGGVVNP NEVFCSVPGRLSLLSSTSK SEQ ID NO: 1891 ENSG00000137474.15 MVILQQGDHVWMDLRLG A*02:03, A*11:01, A*11:02,  QEFDVPIGAVVKLCDSGQV A*24:02, A*24:07, A*24:10,  QVVDDEDNEHWISPQNA A*33:03, B*15:01, B*39:01,  THIKPMHPTSVHGVEDMI B*40:01, B*55:02, B*58:01,  RLGDLNEAGILRNLLIRYRD C*03:02, C*03:04, C*03:67,  HLIYTYTGSILVAVNPYQLLS C*07:02, C*12:02, C*14:02,  IYSPEHIRQYTNKKIGEMPP C*15:02 HIFAIADNCYFNMKRNSRD QCCIISGESGAGKTESTKLIL QFLAAISGQHSWIEQQVLE ATPILEAFGNAKTIRNDNSS RFGKYIDIHFNKRGAIEGAK IEQYLLEKSRVCRQALDERN YHVFYCMLEGMSEDQKKK LGLGQASDYNYLAMGNCI TCEGRVDSQEYANIRSAM KVLMFTDTENWEISKLLAA ILHLGNLQYEARTFENLDA CEVLFSPSLATAASLLEVNP PDLMSCLTSRTLITRGETVS TPLSREQALDVRDAFVKGI YGRLFVWIVDKINAAIYKPP SQDVKNSRRSIGLLDIFGFE NFAVNSFEQLCINFANEHL QQFFVRHVFKLEQEEYDLE SIDWLHIEFTDNQDALDMI ANKPMNIISLIDEESKFPKG TDTTMLHKLNSQHKLNAN YIPPKNNHETQFGINHFAG IVYYETQGFLEKNRDTLHG DIIQLVHSSRNKFIKQIFQA DVAMGAETRKRSPTLSSQF KRSLELLMRTLGACQPFFV RCIKPNEFKKPMLFDRHLC VRQLRYSGMMETIRIRRAG YPIRYSFVEFVERYRVLLPG VKPAYKQGDLRGTCQRMA EAVLGTHDDWQIGKTKIFL KDHHDMLLEVERDKAITD RVILLQKVIRGFKDRSNFLK LKNAATLIQRHWRGHNCR KNYGLMRLGFLRLQALHRS RKLHQQYRLARQRIIQFQA RCRAYLVRKAFRHRLWAVL TVQAYARGMIARRLHQRL RAEYLWRLEAEKMRLAEEE KLRKEMSAKKAKEEAERKH QERLAQLAREDAERELKEK EAARRKKELLEQMERARH EPVNHSDMVDKMFGFLG TSGGLPGQEGQAPSGFED LERGRREMVEEDLDAALPL PDEDEEDLSEYKFAKFAATY FQGTTTHSYTRRPLKQPLLY HDDEGDQLAALAVWITILR FMGDLPEPKYHTAMSDGS EKIPVMTKIYETLGKKTYKR ELQALQGEGEAQLPEGQK KSSVRHKLVHLTLKKKSKLT EEVTKRLHDGESTVQGNS MLEDRPTSNLEKLHFIIGNG ILRPALRDEIYCQISKQLTH NPSKSSYARGWILVSLCVG CFAPSEKFVKYLRNFIHGGP PGYAPYCEERLRRTFVNGT RTQPPSWLELQATKSKKPI MLPVTFMDGTTKTLLTDSA TTAKELCNALADKISLKDRF GFSLYIALFD SEQ ID NO: 1892 ENSG00000138075.7 MGDLSSLTPGGSMGLQV A*02:03, A*02:07, A*11:01,  NRGSQSSLEGAPATAPEPH A*11:02, A*24:02, A*24:07,  SLGILHASYSVSHRVRPW A*24:10, A*33:03, A*34:01,  WDITSCRQQWTRQILKDV B*15:01, B*15:21, B*15:27,  SLYVESGQIMCILGSSGSGK B*27:04, B*38:02, B*39:01,  TTLLDAMSGRLGRAGTFLG B*40:01, B*40:06, B*46:01,  EVYVNGRALRREQFQDCFS B*55:02, B*58:01, C*03:02,  YVLQSDTLLSSLTVRETLHY C*03:04, C*03:67, C*04:01,  TALLAIRRGNPGSFQKKVE C*04:03, C*07:02, C*08:01,  AVMAELSLSHVADRLIGNY C*12:02, C*14:02, C*15:02 SLGGISTGERRRVSIAAQLL QDPKVMLFDEPTTGLDCM TANQIVVLLVELARRNRIVV LTIHQPRSELFQLFDKIAILS FGELIFCGTPAEMLDFFND CGYPCPEHSNPFDFY SEQ ID NO: 1893 ENSG00000142185.12 MEPSALRKAGSEQEEGFE A*02:03, A*11:01, A*11:02,  GLPRRVTDLGMVSNLRRS A*24:02, A*24:07, A*24:10,  NSSLFKSWRLQCPFGNND A*33:03, A*34:01, B*15:01,  KQESLSSWIPENIKKKECVY B*15:27, B*39:01, B*40:01,  FVESSKLSDAGKVVCQCGY B*58:01, C*03:02, C*03:04,  THEQHLEEATKPHTFQGT C*12:02, C*14:02, C*15:02 QWDPKKHVQEMPTDAFG DIVFTGLSQKVKKYVRVSQ DTPSSVIYHLMTQHWGLD VPNLLISVTGGAKNFNMKP RLKSIFRRGLVKVAQTTGA WIITGGSHTGVMKQVGEA VRDFSLSSSYKEGELITIGVA TWGTVHRREGLIHPTGSFP AEYILDEDGQGNLTCLDSN HSHFILVDDGTHGQYGVEI PLRTRLEKFISEQTKERGGV AIKIPIVCVVLEGGPGTLHTI DNATTNGTPCVVVEGSGR VADVIAQVANLPVSDITISLI QQKLSVFFQEMFETFTESRI VEWTKKIQDIVRRRQLLTV FREGKDGQQDVDVAILQA LLKASRSQDHFGHENWDH QLKLAVAWNRVDIARSEIF MDEWQWKPSDLHPTMT AALISNKPEFVKLFLENGVQ LKEFVTWDTLLYLYENLDPS CLFHSKLQMHHVAQVLRE LLGDFTQPLYPRPRHNDRL RLLLPVPHVKLNVQGVSLR SLYKRSSGHVTFTMDPIRD LLIWAIVQNRRELAGIIWA QSQDCIAAALACSKILKELS KEEEDTDSSEEMLALAEEY EHRAIGVFTECYRKDEERA QKLLTRVSEAWGKTTCLQL ALEAKDMKFVSHGGIQAFL TKVWWGQLSVDNGLWR VTLCMLAFPLLLTGLISFREK RLQDVGTPAARARAFFTAP VVVFHLNILSYFAFLCLFAY VLMVDFQPVPSWCECAIY LWLFSLVCEEMRQLFYDPD ECGLMKKAALYFSDFWNK LDVGAILLFVAGLTCRLIPA TLYPGRVILSLDFILFCLRLM HIFTISKTLGPKIIIVKRMMK DVFFFLFLLAVWVVSFGVA KQAILIHNERRVDWLFRGA VYHSYLTIFGQIPGYIDGVN FNPEHCSPNGTDPYKPKCP ESDATQQRPAFPEWLTVLL LCLYLLFTNILLLNLLIAMFN YTFQQVQEHTDQIWKFQR HDLIEEYHGRPAAPPPFILL SHLQLFIKRVVLKTPAKRHK QLKNKLEKNEEAALLSWEI YLKENYLQNRQFQQKQRP EQKIEDISNKVDAMVDLLD LDPLKRSGSMEQRLASLEE QVAQTAQALHWIVRTLRA SGFSSEADVPTLASQKAAE EPDAEPGGRKKTEEPGDSY HVNARHLLYPNCPVTRFPV PNEKVPWETEFLIYDPPFYT AERKDAAAMDPMGENP MGRTGLRGRGSLSCFGPN HTLYPMVTRWRRNEDGAI CRKSIKKMLEVLVVKLPLSE HWALPGGSREPGEMLPRK LKRILRQEHWPSFENLLKC GMEVYKGYMDDPRNTDN AWIETVAVSVHFQDQNDV ELNRLNSNLHACDSGASIR WQVVDRRIPLYANHKTLL QKAAAEFGAHY SEQ ID NO: 1894 ENSG00000142235.4 MRQVLWLCNVCVTARETR A*02:03, A*33:03, B*15:01,  HHLHLPAILDKMPAPGALI B*39:01, B*40:01, C*03:02,  LLAAVSASGCLASPAHPDG C*03:04 FALGRAPLAPPYAVVLISCS GLLAFIFLLLTCLCCKRGDV GFKEFENPEGEDCSGEYTP PAEETSSSQSLPDVYILPLAE VSLPMPAPQPSHSDMTTP LGLSRQHLSYLQEIGSGWF GKVILGEIFSDYTPAQVVVK ELRASAGPLEQRKFISEAQP YRSLQHPNVLQCLGLCVET LPFLLIMEFCQLGDLKRYLR AQRPPEGLSPELPPRDLRTL QRMGLEIARGLAHLHSHN YV SEQ ID NO: 1895 ENSG00000142661.14 MTLPHSLGGAGDPRPPQA A*02:03, A*11:01, A*11:02,  MEVHRLEHRQEEEQKEER A*24:02, A*24:07, A*24:10,  QHSLRMGSSVRRRTFRSSE A*33:03, B*15:01, B*15:27,  EEHEFSAADYALAAALALT B*39:01, B*40:01, B*58:01,  ASSELSWEAQLRRQTSAVE C*03:02, C*03:04, C*03:67,  LEERGQKRVGFGNDWERT C*07:02, C*08:01, C*12:02,  EIAFLQTHRLLRQRRDWKT C*14:02 LRRRTEEKVQEAKELRELCY GRGPWFWIPLRSHAVWE HTTVLLTCTVQASPPPQVT WYKNDTRIDPRLFRAGKYR ITNNYGLLSLEIRRCAIEDSA TYTVRVKNAHGQASSFAK VLVRTYLGKDAGFDSEIFKR STFGPSVEFTSVLKPVFARE KEPFSLSCLFSEDVLDAESIQ WFRDGSLLRSSRRRKILYTD RQASLKVSCTYKEDEGLYM VRVPSPFGPREQSTYVLVR DAEAENPGAPGSPLNVRCL DVNRDCLILTWAPPSDTRG NPITAYTIERCQGESGEWIA CHEAPGGTCRCPIQGLVEG QSYRFRVRAISRVGSSVPSK ASELVVMGDHDAARRKTE IPFDLGNKITISTDAFEDTVT IPSPPTNVHASEIREAYVVL AWEEPSPRDRAPLTYSLEK SVIGSGTWEAISSESPVRSP RFAVLDLEKKKSYVFRVRA MNQYGLSDPSEPSEPIALR GPPATLPPPAQVQAFRDT QTSVSLTWDPVKDPELLGY YIYSRKVGTSEWQTVNNKP IQGTRFTVPGLRTGKEYEFC VRSVSEAGVGESSAATEPIR VKQALATPSAPYGFALLNC GKNEMVIGWKPPKRRGG GKILGYFLDQHDSEELDWH AVNQQPIPTRVCKVSDLHE GHFYEFRARAANWAGVG ELSAPSSLFECKEWTMPQP GPPYDVRASEVRATSLVLQ WEPPLYMGAGPVTGYHVS FQEEGSEQWKPVTPGPISG THLRVSDLQPGKSYVFQVQ AMNSAGLGQPSMPTDPV LLEDKPGAHEIEVGVDEEG FIYLAFEAPEAPDSSEFQWS KDYKGPLDPQRVKIEDKVN KSKVILKEPGLEDLGTYSVIV TDADEDISASHTLTEEELEK LKKLSHEIRNPVIKLISGWNI DILERGEVRLWLEVEKLSPA AELHLIFNNKEIFSSPNRKIN FDREKGLVEVIIQNLSEEDK GSYTAQLQDGKAKNQITLT LVDDDFDKLLRKADAKRRD WKRKQGPYFERPLQWKVT EDCQVQLTCKVTNTKKETR FQWFFQRAEMPDGQYDP ETGTGLLCIEELSKKDKGIYR AMVSDDRGEDDTILDLTG DALDAIFTELGRIGALSATP LKIQGTEEGIRIFSKVKYYNV EYMKTTWFHKDKRLESGD RIRTGTTLDEIWLHILDPKD SDKGKYTLEIAAGKEVRQLS TDLSGQAFEDAMAEHQRL KTLAIIEKNRAKVVRGLPDV ATIMEDKTLCLTCIVSGDPT PEISWLKNDQPVTFLDRYR MEVRGTEVTITIEKVNSEDS GRYGVFVKNKYGSETGQV TISVFKHGDEPKELKSM SEQ ID NO: 1896 ENSG00000143669.9 MSTDSNSLAREFLTDVNRL A*02:03, A*11:01, A*11:02,  CNAVVQRVEAREEEEEETH A*24:02, A*24:07, A*24:10,  MATLGQYLVHGRGFLLLTK A*33:03, A*34:01, B*15:01,  LNSIIDQALTCREELLTLLLSL B*15:27, B*39:01, B*40:01,  LPLVWKIPVQEEKATDFNL B*55:02, B*58:01, C*03:02,  PLSADIILTKEKNSSSQRST C*03:04, C*03:67, C*07:02,  QEKLHLEGSALSSQVSAKV C*12:02, C*14:02, C*15:02 NVFRKSRRQRKITHRYSVR DARKTQLSTSDSEANSDEK GIAMNKHRRPHLLHHFLTS FPKQDHPKAKLDRLATKEQ TPPDAMALENSREIIPRQG SNTDILSEPAALSVISNMN NSPFDLCHVLLSLLEKVCKF DVTLNHNSPLAASVVPTLT EFLAGFGDCCSLSDNLESR VVSAGWTEEPVALIQRML FRTVLHLLSVDVSTAEMM PENLRKNLTELLRAALKIRIC LEKQPDPFAPRQKKTLQEV QEDFVFSKYRHRALLLPELL EGVLQILICCLQSAASNPFY FSQAMDLVQEFIQHHGFN LFETAVLQMEWLVLRDGV PPEASEHLKALINSVMKIM STVKKVKSEQLHHSMCTRK RHRRCEYSHFMHHHRDLS GLLVSAFKNQVSKNPFEET ADGDVYYPERCCCIAVCAH QCLRLLQQASLSSTCVQILS GVHNIGICCCMDPKSVIIPL LHAFKLPALKNFQQHILNIL NKLILDQLGGAEISPKIKKA ACNICTVDSDQLAQLEETL QGNLCDAELSSSLSSPSYRF QGILPSSGSEDLLWKWDAL KAYQNFVFEEDRLHSIQIA NHICNLIQKGNIVVQWKLY NYIFNPVLQRGVELAHHCQ HLSVTSAQSHVCSHHNQC LPQDVLQIYVKTLPILLKSRV IRDLFLSCNGVSQIIELNCLN GIRSHSLKAFETLIISLGEQQ KDASVPDIDGIDIEQKELSS VHVGTSFHHQQAYSDSPQ SLSKFYAGLKEAYPKRRKTV NQDVHINTINLFLCVAFLCV SKEAESDRESANDSEDTSG YDSTASEPLSHMLPCISLES LVLPSPEHMHQAADIWS MCRWIYMLSSVFQKQFYR LGGFRVCHKLIFMIIQKLFR SHKEEQGKKEGDTSVNEN QDLNRISQPKRTMKEDLLS LAIKSDPIPSELGSLKKSADS LGKLELQHISSINVEEVSAT EAAPEEAKLFTSQESETSLQ SIRLLEALLAICLHGARTSQ QKMELELPNQNLSVESILFE MRDHLSQSKVIETQLAKPL FDALLRVALGNYSADFEHN DAMTEKSHQSAEELSSQP GDFSEEAEDSQCCSFKLLVE EEGYEADSESNPEDGETQD DGVDLKSETEGFSASSSPN DLLENLTQGEIIYPEICMLEL NLLSASKAKLDVLAHVFESF LKIIRQKEKNVFLLMQQGT VKNLLGGFLSILTQDDSDF QACQRVLVDLLVSLMSSRT CSEELTLLLRIFLEKSPCTKIL LLGILKIIESDTTMSPSQYLT FPLLHAPNLSNGVSSQKYP GILNSKAMGLLRRARVSRS KKEADRESFPHRLLSSWHI APVHLPLLGQNCWPHLSE GFSVSLWFNVECIHEAEST TEKGKKIKKRNKSLILPDSSF DGTESDRPEGAEYINPGER LIEEGCIHIISLGSKALMIQV WADPHNATLIFRVCMDSN DDMKAVLLAQVESQENIFL PSKWQHLVLTYLQQPQGK RRIHGKISIWVSGQRKPDV TLDFMLPRKTSLSSDSNKTF CMIGHCLSSQEEFLQLAGK WDLGNLLLFNGAKVGSQE AFYLYACGPNHTSVMPCK YGKPVNDYSKYINKEILRCE QIRELFMTKKDVDIGLLIESL SVVYTTYCPAQYTIYEPVIRL KGQMKTQLSQRPFSSKEV QSILLEPHHLKNLQPTEYKT IQGILHEIGGTGIFVFLFARV VELSSCEETQALALRVILSLI KYNQQRVHELENCNGLSM IHQVLIKQKCIVGFYILKTLL EGCCGEDIIYMNENGEFKL DVDSNAIIQDVKLLEELLLD WKIWSKAEQGVWETLLAA LEVLIRADHHQQMFNIKQL LKAQVVHHFLLTCQVLQEY KEGQLTPMPREVCRSFVKII AEVLGSPPDLELLTIIFNFLL AVHPPTNTYVCHNPTNFYF SLHIDGKIFQEKVRSIMYLR HSSSGGRSLMSPGFMVISP SGFTASPYEGENSSNIIPQQ MAAHMLRSRSLPAFPTSSL LTQSQKLTGSLGCSIDRLQ NIADTYVATQSKKQNSLGS SDTLKKGKEDAFISSCESAK TVCEMEAVLSAQVSVSDV PKGVLGFPVVKADHKQLG AEPRSEDDSPGDESCPRRP DYLKGLASFQRSHSTIASLG LAFPSQNGSAAVGRWPSL VDRNTDDWENFAYSLGYE PNYNRTASAHSVTEDCLVP ICCGLYELLSGVLLILPDVLL EDVMDKLIQADTLLVLVNH PSPAIQQGVIKLLDAYFARA SKEQKDKFLKNRGFSLLAN QLYLHRGTQELLECFIEMFF GRHIGLDEEFDLEDVRNM GLFQKWSVIPILGLIETSLYD NILLHNALLLLLQILNSCSKV ADMLLDNGLLYVLCNTVA ALNGLEKNIPMSEYKLLAC DIQQLFIAVTIHACSSSGSQ YFRVIEDLIVMLGYLQNSK NKRTQNMAVALQLRVLQ AAMEFIRTTANHDSENLTD SLQSPSAPHHAVVQKRKSI AGPRKFPLAQTESLLMKM RSVANDELHVMMQRRMS QENPSQATETELAQRLQRL TVLAVNRIIYQEFNSDIIDIL RTPENVTQSKTSVFQTEISE ENIHHEQSSVFNPFQKEIFT YLVEGFKVSIGSSKASGSKQ QWTKILWSCKETFRMQLG RLLVHILSPAHAAQERKQIF EIVHEPNHQEILRDCLSPSL QHGAKLVLYLSELIHNHQG ELTEEELGTAELLMNALKLC GHKCIPPSASTKADLIKMIK EEQKKYETEEGVNKAAWQ KTVNNNQQSLFQRLDSKS KDISKIAADITQAVSLSQGN ERKKVIQHIRGMYKVDLSA SRHWQELIQQLTHDRAV WYDPIYYPTSWQLDPTEG PNRERRRLQRCYLTIPNKYL LRDRQKSEDVVKPPLSYLFE DKTHSSFSSTVKDKAASESI RVNRRCISVAPSRETAGELL LGKCGMYFVEDNASDTVE SSSLQGELEPASFSWTYEEI KEVHKRWWQLRDNAVEIF LTNGRTLLLAFDNTKVRDD VYHNILTNNLPNLLEYGNIT ALTNLWYTGQITNFEYLTH LNKHAGRSFNDLMQYPVF PFILADYVSETLDLNDLLIYR NLSKPIAVQYKEKEDRYVD TYKYLEEEYRKGAREDDPM PPVQPYHYGSHYSNSGTVL HFLVRMPPFTKMFLAYQD QSFDIPDRTFHSTNTTWRL SSFESMTDVKELIPEFFYLPE FLVNREGFDFGVRQNGER VNHVNLPPWARNDPRLFI LIHRQALESDYVSQNICQW IDLVFGYKQKGKASVQAIN VFHPATYFGMDVSAVEDP VQRRALETMIKTYGQTPR QLFHMAHVSRPGAKLNIE GELPAAVGLLVQFAFRETR EQVKEITYPSPLSWIKGLK WGEYVGSPSAPVPVVCFS QPHGERFGSLQALPTRAIC GLSRNFCLLMTYSKEQGVR SMNSTDIQWSAILSWGYA DNILRLKSKQSEPPVNFIQS SQQYQVTSCAWVPDSCQL FTGSKCGVITAYTNRFTSST PSEIEMETQIHLYGHTEEIT SLFVCKPYSILISVSRDGTCII WDLNRLCYVQSLAGHKSP VTAVSASETSGDIATVCDS AGGGSDLRLWTVNGDLV GHVHCREIICSVAFSNQPE GVSINVIAGGLENGIVRLW STWDLKPVREITFPKSNKPI ISLTFSCDGHHLYTANSDGT VIAWCRKDQQRLKQPMFY SFLSSYAAG SEQ ID NO: 1897 ENSG00000143882.5 MSEFWLISAPGDKENLQAL A*02:03, A*11:01, A*11:02,  ERMNTVTSKSNLSYNTKFA A*33:03, B*58:01, C*03:02,  IPDFKVGTLDSLVGLSDELG C*03:04 KLDTFAESLIRRMAQSVVE VMEDSKGKVQEHLLANGV DLTSFVTHFEWD SEQ ID NO: 1898 ENSG00000145214.9 MAAAAEPGARAWLGGGS A*02:03, A*11:01, A*11:02,  PRPGSPACSPVLGSGGRAR A*33:03, B*15:01, B*39:01,  PGPGPGPGPERAGVRAPG B*40:01, C*03:02, C*03:04 PAAAPGHSFRKVTLTKPTF CHLCSDFIWGLAGFLCDVC NFMSHEKCLKHVRIPCTSV APSLVRVPVAHCFGPRGLH KRKFCAVCRKVLEAPALHC EVCELHLHPDCVPFACSDC RQCHQDGHQDHDTHHH HWREGNLPSGARCEVCRK TCGSSDVLAGVRCEWCGV QAHSLCSAALAPECGFGRL RSLVLPPACVRLLPGGFSKT QSFRIVEAAEPGEGGDGA DGSAAVGPGRETQATPES GKQTLKIFDGDDAVRRSQF RLVTVSRLAGAEEVLEAALR AHHIPEDPGHLELCRLPPSS QACDAWAGGKAGSAVISE EGRSPGSGEATPEAWVIRA LPRAQEVLKIYPGWLKVGV AYVSVRVTPKSTARSVVLE VLPLLGRQAESPESFQLVEV AMGCRHVQRTMLMDEQ PLLDRLQDIRQMSVRQVS QTRFYVAESRDVAPHVSLF VGGLPPGLSPEEYSSLLHEA GATKATVVSVSHIYSSQGA VVLDVACFAEAERLYMLLK DMAVRGRLLTALVLPDLLH AKLPPDSCPLLVFVNPKSG GLKGRDLLCSFRKLLNPHQ VFDLTNGGPLPGLHLFSQV PCFRVLVCGGDGTVGWVL GALEETRYRLACPEPSVAIL PLGTGNDLGRVLRWGAGY SGEDPFSVLLSVDEADAVL MDRWTILLDAHEAGSAEN DTADAEP SEQ ID NO: 1899 ENSG00000151025.9 MGAMAYPLLLCLLLAQLGL A*02:03, A*02:07, A*11:01,  GAVGASRDPQGRPDSPRE A*11:02, A*24:02, A*24:07,  RTPKGKPHAQQPGRASAS A*24:10, A*33:03, B*15:01,  DSSAPWSRSTDGTILAQKL B*39:01, B*40:01, B*55:02,  AEEVPMDVASYLYTGDSH B*58:01, C*03:02, C*03:04,  QLKRANCSGRYELAGLPGK C*03:67, C*07:02, C*12:02,  WPALASAHPSLHRALDTLT C*14:02 HATNFLNVMLQSNKSREQ NLQDDLDWYQALVWSLLE GEPSISRAAITFSTDSLSAPA PQVFLQATREESRILLQDLS SSAPHLANATLETEWFHGL RRKWRPHLHRRGPNQGP RGLGHSWRRKDGLGGDKS HFKWSPPYLECENGSYKPG WLVTLSSAIYGLQPNLVPEF RGVMKVDINLQKVDIDQC SSDGWFSGTHKCHLNNSE CMPIKGLGFVLGAYECICK AGFYHPGVLPVNNFRRRG PDQHISGSTKDVSEEAYVC LPCREGCPFCADDSPCFVQ EDKYLRLAIISFQALCMLLD FVSMLVVYHFRKAKSIRAS GLILLETILFGSLLLYFPVVILY FEPSTFRCILLRWARLLGFA TVYGTVTLKLHRVLKVFLSR TAQRIPYMTGGRVMRML AVILLVVFWFLIGWTSSVC QNLEKQISLIGQGKTSDHLI FNMCLIDRWDYMTAVAEF LFLLWGVYLCYAVRTVPSA FHEPRYMAVAVHNELIISAI FHTIRFVLASRLQSDWML MLYFAHTHLTVTVTIGLLLI PKFSHSSNNPRDDIATEAY EDELDMGRSGSYLNSSINS AWSEHSLDPEDIRDELKKL YAQLEIYKRKKMITNNPHL QKKRCSKKGLGRSIMRRIT EIPETVSRQCSKEDKEGAD HGTAKGTALIRKNPPESSG NTGKSKEETLKNRVFSLKKS HSTYDHVRDQTEESSSLPT ESQEEETTENSTLESLSGKK LTQKLKEDSEAESTESVPLV CKSASAHNLSSEKKTGHPR TSMLQKSLSVIASAKEKTLG LAGKTQTAGVEERTKSQKP LPKDKETNRNHSNSDNTET KDPAPQNSNPAEEPRKPQ KSGIMKQQRVNPTTANSD LNPGTTQMKDNFDIGEVC PWEVYDLTPGPVPSESKV QKHVSIVASEMEKNPTFSL KEKSHHKPKAAEVCQQSN QKRIDKAEVCLWESQGQSI LEDEKLLISKTPVLPERAKEE NGGQPRAANVCAGQSEEL PPKAVASKTENENLNQIGH QEKKTSSSEENVRGSYNSS NNFQQPLTSRAEVCPWEF ETPAQPNAGRSVALPASSA LSANKIAGPRKEEIWDSFK V SEQ ID NO: 1900 ENSG00000151229.8 MSRKASENVEYTLRSLSSL A*02:03, A*02:07, A*11:01,  MGERRRKQPEPDAASAAG A*11:02, A*24:10, A*34:01,  ECSLLAAAESSTSLQSAGA B*15:01, B*15:21, B*15:27,  GGGGVGDLERAARRQFQ B*27:04, B*40:01, B*40:06,  QDETPAFVYVVAVFSALGG B*46:01, B*55:02, B*58:01,  FLFGYDTGVVSGAMLLLKR C*01:02, C*03:02, C*03:04,  QLSLDALWQELLVSSTVGA C*03:67, C*04:01, C*04:03,  AAVSALAGGALNGVFGRR C*08:01, C*12:02, C*15:02 AAILLASALFTAGSAVLAAA NNKETLLAGRLVVGLGIGIA SMTVPVYIAEVSPPNLRGR LVTINTLFITGGQFFASVVD GAFSYLQKDGW SEQ ID NO: 1901 ENSG00000151914.13 MAGYLSPAAYLYVEEQEYL A*02:03, A*11:01, A*11:02,  QAYEDVLERYKDERDKVQ A*24:02, A*24:07, A*24:10,  KKTFTKWINQHLMKVRKH A*33:03, A*34:01, B*15:01,  VNDLYEDLRDGHNLISLLEV B*15:27, B*39:01, B*40:01,  LSGDTLPREKGRMRFHRL B*55:02, B*58:01, C*03:02,  QNVQIALDYLKRRQVKLVN C*03:04, C*07:02, C*12:02,  IRNDDITDGNPKLTLGLIWT C*14:02, C*15:02 IILHFQISDIHVTGESEDMS AKERLLLWTQQATEGYAGI RCENFTTCWRDGKLFNAII HKYRPDLIDMNTVAVQSN LANLEHAFYVAEKIGVIRLL DPEDVDVSSPDEKSVITYVS SLYDAFPKVPEGGEGIGAN DVEVKWIEYQNMVNYLIQ WIRHHVTTMSERTFPNNP VELKALYNQYLQFKETEIPP KETEKSKIKRLYKLLEIWIEF GRIKLLQGYHPNDIEKEWG KLIIAMLEREKALRPEVERL EMLQQIANRVQRDSVICE DKLILAGNALQSDSKRLESG VQFQNEAEIAGYILECENLL RQHVIDVQILIDGKYYQAD QLVQRVAKLRDEIMALRN ECSSVYSKGRILTTEQTKLM ISGITQSLNSGFAQTLHPSL TSGLTQSLTPSLTSSSMTSG LSSGMTSRLTPSVTPAYTP GFPSGLVPNFSSGVEPNSL QTLKLMQIRKPLLKSSLLDQ NLTEEEINMKFVQDLLNW VDEMQVQLDRTEWGSDL PSVESHLENHKNVHRAIEE FESSLKEAKISEIQMTAPLKL TYAEKLHRLESQYAKLLNTS RNQERHLDTLHNFVSRAT NELIWLNEKEEEEVAYDWS ERNTNIARKKDYHAELMRE LDQKEENIKSVQEIAEQLLL ENHPARLTIEAYRAAMQT QWSWILQLCQCVEQHIKE NTAYFEFFNDAKEATDYLR NLKDAIQRKYSCDRSSSIHK LEDLVQESMEEKEELLQYK STIANLMGKAKTIIQLKPRN SDCPLKTSIPIKAICDYRQIEI TIYKDDECVLANNSHRAK WKVISPTGNEAMVPSVCF TVPPPNKEAVDLANRIEQQ YQNVLTLWHESHINMKSV VSWHYLINEIDRIRASNVAS IKTMLPGEHQQVLSNLQSR FEDFLEDSQESQVFSGSDIT QLEKEVNVCKQYYQELLKS AEREEQEESVYNLYISEVRN IRLRLENCEDRLIRQIRTPLE RDDLHESVFRITEQEKLKKE LERLKDDLGTITNKCEEFFS QAAASSSVPTLRSELNVVL QNMNQVYSMSSTYIDKLK TVNLVLKNTQAAEALVKLY ETKLCEEEAVIADKNNIENLI STLKQWRSEVDEKRQVFH ALEDELQKAKAISDEMFKT YKERDLDFDWHKEKADQL VERWQNVHVQIDNRLRDL EGIGKSLKYYRDTYHPLDD WIQQVETTQRKIQENQPE NSKTLATQLNQQKMLVSEI EMKQSKMDECQKYAEQYS ATVKDYELQTMTYRAMVD SQQKSPVKRRRMQSSADLI IQEFMDLRTRYTALVTLMT QYIKFAGDSLKRLEEEEKSL EEEKKEHVEKAKELQKWVS NISKTLKDAEKAGKPPFSK QKISSEEISTKKEQLSEALQT IQLFLAKHGDKMTDEERNE LEKQVKTLQESYNLLFSESL KQLQESQTSGDVKVEEKLD KVIAGTIDQTTGEVLSVFQ AVLRGLIDYDTGIRLLETQL MISGLISPELRKCFDLKDAK SHGLIDEQILCQLKELSKAK EIISAASPTTIPVLDALAQS MITESMAIKVLEILLSTGSLV IPATGEQLTLQKAFQQNLV SSALFSKVLERQNMCKDLI DPCTSEKVSLIDMVQRSTL QENTGMWLLPVRPQEGG RITLKCGRNISILRAAHEGLI DRETMFRLLSAQLLSGGLI NSNSGQRMTVEEAVREGV IDRDTASSILTYQVQTGGII QSNPAKRLTVDEAVQCDLI TSSSALLVLEAQRGYVGLI WPHSGEIFPTSSSLQQELIT NELAYKILNGRQKIAALYIP ESSQVIGLDAAKQLGIIDNN TASILKNITLPDKMPDLGDL EACKNARRWLSFCKFQPST VHDYRQEEDVFDGEEPVT TQTSEETKKLFLSYLMINSY MDANTGQRLLLYDGDLDE AVGMLLEGCHAEFDGNTA IKECLDVLSSSGVFLNNASG REKDECTATPSSFNKCHCG EPEHEETPENRKCAIDEEFN EMRNTVINSEFSQSGKLAS TISIDPKVNSSPSVCVPSLIS YLTQTELADISMLRSDSENI LTNYENQSRVETNERANEC SHSKNIQNFPSDLIENPIMK SKMSKFCGVNETENEDNT NRDSPIFDYSPRLSALLSHD KLMHSQGSFNDTHTPESN GNKCEAPALSFSDKTMLSG QRIGEKFQDQFLGIAAINIS LPGEQYGQKSLNMISSNP QVQYHNDKYISNTSGEDEK THPGFQQMPEDKEDESEIE EYSCAVTPGGDTDNAIVSL TCATPLLDETISASDYETSLL NDQQNNTGTDTDSDDDF YDTPLFEDDDHDSLLLDGD DRDCLHPEDYDTLQEEND ETASPADVFYDVSKENENS MVPQGAPVGSLSVKNKAH CLQDFLMDVEKDELDSGE KIHLNPVGSDKVNGQSLET GSERECTNILEGDESDSLTD YDIVGGKESFTASLKFDDSG SWRGRKEEYVTGQEFHSD TDHLDSMQSEESYGDYIYD SNDQDDDDDDGIDEEGG GIRDENGKPRCQNVAEDM DIQLCASILNENSDENENIN TMILLDKMHSCSSLEKQQR VNVVQLASPSENNLVTEKS NLPEYTTEIAGKSKENLLNH EMVLKDVLPPIIKDTESEKT FGPASISHDNNNISSTSELG TDLANTKVKLIQGSELPELT DSVKGKDEYFKNMTPKVD SSLDHIICTEPDLIGKPAEES HLSLIASVTDKDPQGNGSD LIKGRDGKSDILIEDETSIQK MYLGEGEVLVEGLVEEENR HLKLLPGKNTRDSFKLINSQ FPFPQITNNEELNQKGSLK KATVTLKDEPNNLQIIVSKS PVQFENLEEIFDTSVSKEIS DDITSDITSWEGNTHFEESF TDGPEKELDLFTYLKHCAK NIKAKDVAKPNEDVPSHVL ITAPPMKEHLQLGVNNTKE KSTSTQKDSPLNDMIQSN DLCSKESISGGGTEISQFTP ESIEATLSILSRKHVEDVGK NDFLQSERCANGLGNDNS SNTLNTDYSFLEINNKKERI EQQLPKEQALSPRSQEKEV QIPELSQVFVEDVKDILKSR LKEGHMNPQEVEEPSACA DTKILIQNLIKRITTSQLVNE ASTVPSDSQMSDSSGVSP MTNSSELKPESRDDPFCIG NLKSELLLNILKQDQHSQKI TGVFELMRELTHMEYDLEK RGITSKVLPLQLENIFYKLLA DGYSEKIEHVGDFNQKACS TSEMMEEKPHILGDIKSKE GNYYSPNLETVKEIGLESST VWASTLPRDEKLKDLCNDF PSHLECTSGSKEMASGDSS TEQFSSELQQCLQHTEKM HEYLTLLQDMKPPLDNQES LDNNLEALKNQLRQLETFE LGLAPIAVILRKDMKLAEEF LKSLPSDFPRGHVEELSISH QSLKTAFSSLSNVSSERTKQ IMLAIDSEMSKLAVSHEEFL HKLKSFSDWVSEKSKSVKD IEIVNVQDSEYVKKRLEFLK NVLKDLGHTKMQLETTAF DVQFFISEYAQDLSPNQSK QLLRLLNTTQKCFLDVQES VTTQVERLETQLHLEQDLD DQKIVAERQQEYKEKLQGI CDLLTQTENRLIGHQEAFM IGDGTVELKKYQSKQEELQ KDMQGSAQALAEVVKNTE NFLKENGEKLSQEDKALIE QKLNEAKIKCEQLNLKAEQ SKKELDKVVTTAIKEETEKV AAVKQLEESKTKIENLLDW LSNVDKDSERAGTKHKQVI EQNGTHFQEGDGKSAIGE EDEVNGNLLETDVDGQVG TTQENLNQQYQKVKAQHE KIISQHQAVIIATQSAQVLL EKQGQYLSPEEKEKLQKN MKELKVHYETALAESEKKM KLTHSLQEELEKFDADYTEF EHWLQQSEQELENLEAGA DDINGLMTKLKRQKSFSED VISHKGDLRYITISGNRVLE AAKSCSKRDGGKVDTSAT HREVQRKLDHATDRFRSLY SKCNVLGNNLKDLVDKYQ HYEDASCGLLAGLQACEAT ASKHLSEPIAVDPKNLQRQ LEETKALQGQISSQQVAVE KLKKTAEVLLDARGSLLPAK NDIQKTLDDIVGRYEDLSKS VNERNEKLQITLTRSLSVQD GLDEMLDWMGNVESSLK EQDVGTGYCRSSEQYKCH E SEQ ID NO: 1902 ENSG00000152359.10 MSSDEEKYSLPVVQNDSSR A*02:03, A*11:01, A*11:02,  GSSVSSNLQEEYEELLHYAI A*24:02, A*24:10, A*33:03,  VTPNIEPCASQSSHPKGEL A*34:01, B*39:01, B*40:01,  VPDVRISTIHDILHSQGNNS B*55:02, C*03:02, C*03:04,  EVRETAIEVGKGCDFHISSH C*12:02 SKTDESSPVLSPRKPSHPV MDFFSSHLLADSSSPATNS SHTDAHEILVSDFLVSDENL QKMENVLDLWSSGLKTNII SELSKWRLNFIDWHRME MRKEKEKHAAHLKQLCNQ INELKELQKTFEISIGRKDEV ISSLSHAIGKQKEKIELMRTF FHWRIGHVRARQDVYEGK LADQYYQRTLLKKVWKVW RSVVQKQWKDVVERACQ ARAEEVCIQISNDYEAKVA MLSGALENAKAEIQRMQH EKEHFEDSMKKAFMRGVC ALNLEAMTIFQNRNDAGI DSTNNKKEEYGPGVQGKE HSAHLDPSAPPMPLPVTSP LLPSPPAAVGGASATAVPS AASMTSTRAASASSVHVP VSALGAGSAATAASEEMY VPRVVTSAQQKAGRTITAR ITGRCDFASKNRISSSLAIM GVSPPMSSVVVEKHHPVT VQTIPQATAAKYPRTIHPES STSASRSLGTRSAHTQSLTS VHSIKVVD SEQ ID NO: 1903 ENSG00000153046.13 MASEELYEVERIVDKRKNK A*02:03, A*11:01, A*11:02,  KGKTEYLVRWKGYDSEDD A*33:03, B*15:01, C*03:02,  TWEPEQHLVNCEEYIHDF C*07:02, C*15:02 NRRHTEKQKESTLTRTNRT SPNNARKQISRSTNSNFSK TSPKALVIGKDHESKNSQLF AASQKFRKNTAPSLSSRKN SEQ ID NO: 1904 ENSG00000154556.13 MSYYQRPFSPSAYSLPASL A*02:03, A*11:01, A*11:02,  NSSIVMQHGTSLDSTDTYP A*24:10, A*33:03, B*15:01,  QHAQSLDGTTSSSIPLYRSS B*15:27, B*39:01, B*58:01,  EEEKRVTVIKAPHYPGIGPV C*03:02, C*03:04, C*07:02,  DESGIPTAIRTTVDRPKDW C*12:02, C*14:02, C*15:02 YKTMFKQIHMVHKPDDDT DMYNTPYTYNAGLYNPPY SAQSHPAAKTQTYRPLSKS HSDNSPNAFKDASSPVPPP HVPPPVPPLRPRDRSSTEK HDWDPPDRKVDTRKFRSE PRSIFEYEPGKSSILQHERPA SLYQSSIDRSLERPMSSAS MASDFRKRRKSEPAVGPP RGLGDQSASRTSPGRVDLP GSSTTLTKSFTSSSPSSPSRA KGGDDSKICPSLCSYSGLN GNPSSELDYCSTYRQHLDV PRDSPRAISFKNGWQMAR QNAEIWSSTEETVSPKIKSR SCDDLLNDDCDSFPDPKVK SESMGSLLCEEDSKESCPM AWGSPYVPEVRSNGRSRIR HRSARNAPGFLKMYKKM HRINRKDLMNSEVICSVKS RILQYESEQQHKDLLRAWS QCSTEEVPRDMVPTRISEF EKLIQKSKSMPNLGDDMLS PVTLEPPQNGLCPKRRFSIE YLLEEENQSGPPARGRRGC QSNALVPIHIEVTSDEQPR AHVEFSDSDQDGVVSDHS DYIHLEGSSFCSESDFDHFS FTSSESFYGSSHHHHHHHH HHHRHLISSCKGRCPASYT RFTTMLKHERARHENTEEP RRQEMDPGLSKLAFLVSPV PFRRKKNSAPKKQTEKAKC KASVFEALDSALKDICDQIK AEKKRGSLPDNSILHRLISEL LPDVPERNSSLRALRRSPLH QPLHPLPPDGAIHCPPYQN DCGRMPRSASFQDVDTAN SSCHHQDRGGAL SEQ ID NO: 1905 ENSG00000155275.14 MAEVGRTGISYPGALLPQG A*02:03, A*11:01, A*11:02,  FWAAVEVWLERPQVANK A*24:02, A*24:10, A*33:03,  RLCGARLEARWSAALPCAE B*15:01, B*15:27, B*39:01,  ARGPGTSAGSEQKERGPG B*40:01, B*55:02, B*58:01,  PGQGSPGGGPGPRSLSGP C*03:02, C*14:02, C*15:02 EQGTACCELEEAQGQCQQ EEAQREAASVPLRDSGHP GHAEGREGDFPAADLDSL WEDFSQSLARGNSELLAFL TSSGAGSQPEAQRELDVVL RTVIPKTSPHCPLTTPRREIV VQDVLNGTITFLPLEEDDE GNLKVKMSNVYQIQLSHS KEEWFISVLIFCPERWHSD GIVYPKPTWLGEELLAKLAK WSVENKKSDFKSTLSLISIM KYSKAYQELKEKYKEMVKV WPEVTDPEKFVYEDVAIAA YLLILWEEERAERRLTARQS FVDLGCGNGLLVHILSSEG HPGRGIDVRRRKIWDMYG PQTQLEEDAITPNDKTLFP DVDWLIGNHSDELTPWIP VIAARSSYNCRFFVLPCCFF DFIGRYSRRQSKKTQYREYL DFIKEVGFTCGFHVDEDCL RIPSTKRVCLVGKSRTYPSS REASVDEKRTQYIKSRRGC PVSPPGWELSPSPRWVAA GSAGHCDGQQALDARVG CVTRAWAAEHGAGPQAE GPWLPGFHPREKAERVRN CAALPRDFIDQVVLQVANL LLGGKQLNTRSSRNGSLKT WNGGESLSLAEVANELDT ETLRRLKRECGGLQTLLRNS HQVFQVVNGRVHIRDWR EETLWKTKQPEAKQRLLSE ACKTRLCWFFMHHPDGC ALSTDCCPFAHGPAELRPP RTTPRKKIS SEQ ID NO: 1906 ENSG00000155506.12 MATQVEPLLPGGATLLQA A*02:03 EEHGGLVRKKPPPAPEGKG EPGPNDVRGGEPDGSARR PRPPCAKPHKEGTGQQER ESPRPLQLPGAEGPAISDG EEGGGEPGAGGGAAGAA GAGRRDFVEAPPPKVNPW TKNALPPVLTTVNGQ SEQ ID NO: 1907 ENSG00000157514.12 MNTEMYQTPMEVAVYQL A*02:03, A*24:02, A*24:07,  HNFSISFFSSLLGGDVVSVK A*24:10, B*15:01, C*03:02,  LD C*03:04, C*03:67, C*12:02,  C*15:02 SEQ ID NO: 1908 ENSG00000158321.11 MDGPTRGHGLRKKRRSRS A*02:03, A*24:10, B*15:01,  QRDRERRSRGGLGAGAAG B*15:27, B*39:01, B*58:01,  GGGAGRTRALSLASSSGSD C*03:02, C*03:04, C*03:67,  KEDNGKPPSSAPSRPRPPR C*12:02, C*14:02, C*15:02 RKRRESTSAEEDIIDGFAMT SFVTFEALEKDVALKPQER VEKRQTPLTKKKREALTNG LSFHSKKSRLSHPHHYSSDR ENDRNLCQHLGKRKKMPK ALRQLKPGQNSCRDSDSES ASGESKGFHRSSSRERLSDS SAPSSLGTGYFCDSDSDQE EKASDASSEKLFNTVIVNKD PELGVGTLPEHDSQDAGPI VPKISGLERSQEKSQDCCKE PIFEPVVLKDPCPQVAQPIP QPQTEPQLRAPSPDPDLV QRTEAPPQPPPLSTQPPQ GPPEAQLQPAPQPQVQRP PRPQSPTQLLHQNLPPVQ AHPSAQSLSQPLSAYNSSSL SLNSLSSSRSSTPAKTQPAP PHISHHPSASPFPLSLPNHS PLHSFTPTLQPPAHSHHPN MFAPPTALPPPPPLT SEQ ID NO: 1909 ENSG00000158486.9 MGATGRLELTLAAPPHPG A*02:03, A*02:07, A*11:01,  PAFQRSKARETQGEEEGSE A*11:02, A*24:02, A*24:07,  MQIAKSDSIHHMSHSQGQ A*24:10, A*33:03, A*34:01,  PELPPLPASANEEPSGLYQT B*15:01, B*15:21, B*15:27,  VMSHSFYPPLMQRTSWTL B*27:04, B*38:02, B*39:01,  AAPFKEQHHHRGPSDSIA B*40:01, B*40:06, B*46:01,  NNYSLMAQDLKLKDLLKVY B*51:01, B*55:02, B*58:01,  QPATISVPRDRTGQGLPSS C*01:02, C*03:02, C*03:04,  GNRSSSEPMRKKTKFSSRN C*03:67, C*04:01, C*04:03,  KEDSTRIKLAFKTSIFSPMK C*07:02, C*08:01, C*12:02,  KEVKTSLTFPGSRPMSPEQ C*14:02, C*15:02 QLDVMLQQEMEMESKEK KPSESDLERYYYYLTNGIRK DMIAPEEGEVMVRISKLIS NTLLTSPFLEPLMVVLVQE KENDYYCSLMKSIVDYILM DPMERKRLFIESIPRLFPQR VIRAPVPWHSVYRSAKKW NEEHLHTVNPMMLRLKEL WFAEFRDLRFVRTAEILAG KLPLQPQEFWDVIQKHCLE AHQTLLNKWIPTCAQLFTS RKEHWIHFAPKSNYDSSRN IEEYFASVASFMSLQLRELV IKSLEDLVSLFMIHKDGNDF KEPYQEMKFFIPQLIMIKLE VSEPIIVFNPSFDGCWELIR DSFLEIIKNSNGIPKLKYIPLK FSFTAAAADRQCVKAAEP GEPSMHAAATAMAELKGY NLLLGTVNAEEKLVSDFLIQ TFKVFQKNQVGPCKYLNV YKKYVDLLDNTAEQNIAAF LKENHDIDDFVTKINAIKKR RNEIASMNITVPLAMFCLD ATALNHDLCERAQNLKDH LIQFQVDVNRDTNTSICNQ YSHIADKVSEVPANTKELVS LIEFLKKSSAVTVFKLRRQLR DASERLEFLMDYADLPYQI EDIFDNSRNLLLHKRDQAE MDLIKRCSEFELRLEGYHRE LESFRKREVMTTEEMKHN VEKLNELSKNLNRAFAEFEL INKEEELLEKEKSTYPLLQA MLKNKVPYEQLWSTAYEF SIKSEEWMNGPLFLLNAEQ IAEEIGNMWRTTYKLIKTLS DVPAPRRLAENVKIKIDKFK QYIPILSISCNPGMKDRHW QQISEIVGYEIKPTETTCLSN MLEFGFGKFVEKLEPIGAA ASKEYSLEKNLDRMKLDW VNVTFSFVKYRDTDTNILC AIDDIQMLLDDHVIKTQTM CGSPFIKPIEAECRKWEEKLI RIQDNLDAWLKCQATWLY LEPIFSSEDIIAQMPEEGRK FGIVDSYWKSLMSQAVKD NRILVAADQPRMAEKLQE ANFLLEDIQKGLNDYLEKKR LFFPRFFFLSNDELLEILSETK DPLRVQPHLKKCFEGIAKLE FTDNLEIVGMISSEKETVPFI QKIYPANAKGMVEKWLQ QVEQMMLASMREVIGLGI EAYVKVPRNHWVLQWPG QVVICVSSIFWTQEVSQAL AENTLLDFLKKSNDQIAQIV QLVRGKLSSGARLTLGALT VIDVHARDVVAKLSEDRVS DLNDFQWISQLRYYWVAK DVQVQIITTEALYGYEYLGN SPRLVITPLTDRCYRTLMGA LKLNLGGAPEGPAGTGKTE TTKDLAKALAKQCVVFNCS DGLDYKAMGKFFKGLAQA GAWACFDEFNRIEVEVLSV VAQQILSIQQAIIRKLKTFIF EGTELSLNPTCAVFIT SEQ ID NO: 1910 ENSG00000159263.11 MKEKSKNAAKTRREKENG A*02:03, A*24:02, A*24:07,  EFYELAKLLPLPSAITSQLDK A*24:10, A*34:01, B*15:01,  ASIIRLTTSYLKMRAVFPEG B*15:21, B*15:27, B*38:02,  LGDA B*39:01, B*40:01, B*40:06,  B*51:01, B*55:02, C*14:02,  C*15:02 SEQ ID NO: 1911 ENSG00000159788.14 MFRAGEASKRPLPGPSPPR A*02:03, A*11:01, A*11:02,  VRSVEVARGRAGYGFTLSG A*24:10, A*33:03, A*34:01,  QAPCVLSCVMRGSPADFV B*15:01, B*40:01, B*55:02,  GLRAGDQILAVNEINVKKA C*15:02 SHEDVVKLIGKCSGVLHMV IAEGVGRFESCSSDEEGGLY EGKGWLKPKLDSKALGINR AERVVEEMQSGGIFNMIF ENPSLCASNSEPLKLKQRSL SESAATRFDVGHESINNPN PNMLSKEEISKVIHDDSVFS IGLESHDDFALDASILNVA MIVGYLGSIELPSTSSNLES DSLQAIRGCMRRLRAEQKI HSLVTMKIMHDCVQLSTD KAGVVAEYPAEKLAFSAVC PDDRRFFGLVTMQTNDD GSLAQEEEGALRTSCHVF MVDPDLFNHKIHQGIARR FGFECTADPDTNGCLEFPA SSLPVLQFISVLYRDMGELI EGMRARAFLDGDADAHQ NNSTSSNSDSGIGNFHQEE KSNRVLVVD SEQ ID NO: 1912 ENSG00000160200.13 MPSETPQAEVGPTGCPHR A*02:03, A*11:01, A*11:02,  SGPHSAKGSLEKGSPEDKE A*24:10, A*33:03, B*15:01,  AKEPLWIRPDAPSRCTWQ B*38:02, B*39:01, B*40:01,  LGRPASESPHHHTAPAKSP B*58:01, C*03:02, C*03:04,  KILPDILKKIGDTPMVRINKI C*07:02, C*14:02 GKKFGLKCELLAKCEFFNA GGSVKDRISLRMIEDAERD GTLKPGDTIIEPTSGNTGIG LALAAAVRGYRCIIVMPEK MSSEKVDVLRALGAEIVRT PTNARFDSPESHVGVAWR LKNEIPNSHILDQYRNASN PLAHYDTTADEILQQCDGK LDMLVASVGTGGTITGIAR KLKEKCPGCRIIGVDPEGSIL AEPEELNQTEQTTYEVEGI GYDFIPTVLDRTVVDKWFK SNDEEAFTFARMLIAQEGL LCGGSAGSTVAVAVKAAQ ELQEGQRCVVILPDSVRNY MTKFLSDRWMLQKGFLKE EDLTEKKPWWWHLRVQE LGLSAPLTVLPTITCGHTIEIL REKGFDQAPVVDEAGVILG MVTLGNMLSSLLAGKVQP SDQVGKVIYKQFKQIRLTD TLGRLSHILEMDHFALVVH EQIQYHSTGKSSQRQMVF GVVTAIDLLNFVAAQERDQ K SEQ ID NO: 1913 ENSG00000160799.7 MQDGRKGGAYAGKMEAT A*02:03 TAGVGRLEEEALRRKERLK ALREKTG SEQ ID NO: 1914 ENSG00000160838.9 MSSEQSAPGASPRAPRPG A*02:03, A*11:01, A*11:02,  TQKSSGAVTKKGERAAKEK A*24:02, A*24:07, A*24:10,  PATVLPPVGEEEPKSPEEY B*40:01, B*55:02, C*01:02,  QCSGVLETDFAELCTRWG C*03:02, C*04:01, C*04:03,  YTDFPKVVNRPRPHPPFVP C*07:02, C*15:02 SASLSEKATLDDPRLSGSCS LNSLESKYVFFRPTIQVELE QEDSKSVKEIYIRGWKVEE RILGVFSKCLPPLTQLQAIN LWKVGLTDKTLTTFIELLPL CSSTLRKVSLEGNPLPEQSY HKL SEQ ID NO: 1915 ENSG00000164093.11 METNCRKLVSACVQLGVQ A*11:01, A*11:02, A*33:03 PAAVECLFSKDSEIKKVEFT DSPESRKEAASSKFFPRQH SEQ ID NO: 1916 ENSG00000164764.10 MRTLWMALCALSRLWPG A*11:01, A*11:02, A*24:10,  AQAGCAEAGRCCPGRDPA A*33:03, B*55:02, C*03:02,  CFARGWRLDRVYGTCFCD C*03:04 QACRFTGDCCFDYDRACP ARPCFVGEWSPWSGCAD QCKPTTRVRRRSVQQEPQ NGGAPCPPLEERAGCLEYS TPQGQDCGHTYVPAFITTS AFNKERTRQATSPHWSTH TEDAGYCMEFKTESLTPHC ALENWPLTRWMQYLREG YTVCVDCQPPAMNSVSLR CSGDGLDSDGNQTLHWQ AIGNPRCQGTWKKVRRVD QCSCPAVHSFIFI SEQ ID NO: 1917 ENSG00000164830.13 MDYLTTFTEKSGRLLRGTA A*33:03 NRLLGFGGGGEARQVRFE DYLREPAQGDLGCGSPPH RPPAPSSPEGP SEQ ID NO: 1918 ENSG00000166689.10 MAAATVGRDTLPEHWSY A*33:03 GVCRDGRVFFINDQLRCTT WLHPRTGEPVNSGHMIRS DLPRGWEE SEQ ID NO: 1919 ENSG00000167157.9 MDSAAAAFALDKPALGPG A*11:01, A*11:02, C*03:02,  PPPPPPALGPGDCAQARK C*03:04, C*03:67 NFSVSHLLDLEEVAAAGRL AARPGARAEAREGAAREP SGGSSGSEAAPQ SEQ ID NO: 1920 ENSG00000167632.10 MSVPDYMQCAEDHQTLL A*02:03, A*02:07, A*11:01,  VVVQPVGIVSEENFFRIYKR A*11:02, A*24:02, A*24:07,  ICSVSQISVRDSQRVLYIRYR A*24:10, A*33:03, B*15:01,  HHYPPENNEWGDFQTHR B*15:27, B*39:01, B*40:01,  KVVGLITITDCFSAKDWPQ B*55:02, B*58:01, C*03:02,  TFEKFHVQKEIYGSTLYDSR C*03:04, C*03:67, C*07:02,  LFVFGLQGEIVEQPRTDVA C*12:02, C*14:02, C*15:02 FYPNYEDCQTVEKRIEDFIE SLFIVLESKRLDRATDKSGD KIPLLCVPFEKKDFVGLDTD SRHYKKRCQGRMRKHVG DLCLQAGMLQDSLVHYH MSVELLRSVNDFLWLGAA LEGLCSASVIYHYPGGTGG KSGARRFQGSTLPAEAANR HRPGALTTNGINPDTSTEI GRAKNCLSPEDIIDKYKEAIS YYSKYKNAGVIELEACIKAV RVLAIQKRSMEASEFLQNA VYINLRQLSEEEKIQRYSILS ELYELIGFHRKSAFFKRVAA MQCVAPSIAEPGWRACYK LLLETLPGYSLSLDPKDFSR GTHRGWAAVQMRLLHEL VYASRRMGNPALSVRHLSF LLQTMLDFLSDQEKKDVA QSLENYTSKCPGTMEPIAL PGGLTLPPVPFTKLPIVRHV KLLNLPASLRPHKMKSLLG QNVSTKSPFIYSPIIAHNRG EERNKKIDFQWVQGDVCE VQLMVYNPMPFELRVEN MGLLTSGVEFESLPAALSLP AESGLYPVTLVGVPQTTGTI TVNGYHTTVFGVFSDCLLD NLPGIKTSGSTVEVIPALPR LQISTSLPRSAHSLQPSSGD EISTNVSVQLYNGESQQLII KLENIGMEPLEKLEVTSKVL TTKEKLYGDFLSWKLEETLA QFPLQPGKVATFTINIKVKL DFSCQENLLQDLSDDGISV SGFPLSSPFRQVVRPRVEG KPVNPPESNKAGDYSHVKT LEAVLNFKYSGGPGHTEGY YRNLSLGLHVEVEPSVFFTR VSTLPATSTRQCHLLLDVF NSTEHELTVSTRSSEALILH AGECQRMAIQVDKFNFES FPESPGEKGQFANPKQLEE ERREARGLEIHSKLGICWRI PSLKRSGEASVEGLLNQLVL EHLQLAPLQWDVLVDGQP CDREAVAACQVGDPVRLE VRLTNRSPRSVGPFALTVV PFQDHQNGVHNYDLHDT VSFVGSSTFYLDAVQPSGQ SACLGALLFLYTGDFFLHIRF HEDSTSKELPPSWFCLPSV HVCALEAQA SEQ ID NO: 1921 ENSG00000170615.10 MDHAEENEILAATQRYYVE A*02:03, A*02:07, A*11:01,  RPIFSHPVLQERLHTKDKVP A*11:02, A*24:02, A*24:07,  DSIADKLKQAFTCTPKKIRN A*24:10, A*33:03, A*34:01,  IIYMFLPITKWLPAYKFKEY B*15:01, B*15:21, B*15:27,  VLGDLVSGISTGVLQLPQG B*27:04, B*38:02, B*39:01,  LAFAMLAAVPPIFGLYSSFY B*40:01, B*40:06, B*46:01,  PVIMYCFLGTSRHISIGPFA B*51:01, B*55:02, B*58:01,  VISLMIGGVAVRLVPDDIVI C*01:02, C*03:02, C*03:04,  PGGVNATNGTEARDALRV C*03:67, C*04:01, C*04:03,  KVAMSVTLLSGIIQFCLGVC C*08:01, C*12:02, C*14:02,  RFGFVAIYLTEPLVRGFTTA C*15:02 AAVHVFTSMLKYLFGVKTK RYSGIFSVVYSTVAVLQNV KNLNVCSLGVGLMVFGLLL GGKEFNERFKEKLPAPIPLE FFAVVMGTGISAGFNLKES YNVDVVGTLPLGLLPPANP DTSLFHLVYVDAIAIAIVGFS VTISMAKTLANKHGYQVD GNQELIALGLCNSIGSLFQT FSISCSLSRSLVQEGTGGKT QLAGCLASLMILLVILATGF LFESLPQAVLSAIVIVNLKG MFMQFSDLPFFWRTSKIEL TIWLTTFVSSLFLGLDYGLIT AVIIALLTVIYRTQS SEQ ID NO: 1922 ENSG00000171680.16 MHYDGHVRFDLPPQGSVL A*02:03, A*02:07, A*11:01,  ARNVSTRSCPPRTSPAVDL A*11:02, A*24:10, A*33:03,  EEEEEESSVDGKGDRKSTG B*15:01, B*39:01, B*40:01,  LKLSKKKARRRHTDDPSKE B*58:01, C*03:02, C*03:04,  CFTLKFDLNVDIETEIVPAM C*07:02, C*12:02, C*14:02,  KKKSLGEVLLPVFERKGIAL C*15:02 GKVDIYLDQSNTPLSLTFEA YRFGGHYLRVKAPAKPGDE GKVEQGMKDSKSLSLPILR PAGTGPPALERVDAQSRRE SLDILAPGRRRKNMSEFLG EASIPGQEPPTPSSCSLPSG SSGSTNTGDSWKNRAASR FSGFFSSGPSTSAFGREVDK MEQLEGKLHTYSLFGLPRL PRGLRFDHDSWEEEYDED EDEDNACLRLEDSWRELID GHEKLTRRQCHQQEAVW ELLHTEASYIRKLRVIINLFLC CLLNLQESGLLCEVEAERLF SNIPEIAQLHRRLWASVMA PVLEKARRTRALLQPGDFL KGFKMFGSLFKPYIRYCME EEGCMEYMRGLLRDNDLF RAYITWAEKHPQCQRLKLS DMLAKPHQRLTKYPLLLKS VLRKTEEPRAKEAVVAMIG SVERFIHHVNACMRQRQE RQRLAAVVSRIDAYEVVES SSDEVDKLLKEFLHLDLTAPI PGASPEETRQLLLEGSLRM KEGKDSKMDVYCFLFTDLL LVTKAVKKAERTRVIRPPLL VDKIVCRELRDPGSFLLIYLN EFHSAVGAYTFQASGQALC RGWVDTIYNAQNQLQQL RAQEPPGSQQPLQSLEEEE DEQEEEEEEEEEEEEGEDS GTSAASSPTIMRKSSGSPD SQHCASDGSTETLAMVVV EPGDTLSSPEEDSGPFSSQS DETSLSTTASSATPTSELLPL GPVDGRSCSMDSAYGTLS PTSLQDFVAPGPMAELVP RAPESPRVPSPPPSPRLRRR TPVQLLSCPPHLLKSKSEAS LLQLLAGAGTHGTPSAPSR SLSELCLAVPAPGIRTQGSP QEAGPSWDCRGAPSPGSG PGLVGCLAGEPAGSHRKRC GDLPSGASPRVQPEPPPGV SAQHRKLTLAQLYRIRTTLL LNSTLTASEV SEQ ID NO: 1923 ENSG00000171791.10 MAHAGRTGYDNREIVMK A*02:03, A*11:01, A*11:02,  YIHYKLSQRGYEWDAGDV A*24:02, A*24:07, A*24:10,  GAAPPGAAPAPGIFSSQPG A*33:03, A*34:01, B*15:21,  HTPHPAASRDPVARTSPLQ B*27:04, B*40:01, B*40:06,  TPAAPGAAAGPALSPVPPV B*46:01, B*55:02, B*58:01,  VHLTLRQAGDDFSRRYRRD C*01:02, C*03:02, C*04:01,  FAEMSSQLHLTPFTARGRF C*04:03, C*14:02 ATVVEELFRDGVNWGRIV AFFEFGGVMCVESVNREM SPLVDNIALWMTEYLNRHL HTWIQDNGGWDAFVELY GPS SEQ ID NO: 1924 ENSG00000172765.12 MKRGTSLHSRRGKPEAPK A*02:03, A*33:03, C*03:02,  GSPQINRKSGQEMTAVM C*03:04 QSGRPRSSSTTDAPTSSAM MEIACAAAAAAAACLPGE EGTAE SEQ ID NO: 1925 ENSG00000174672.11 MTSTGKDGGAQHAQYVG A*02:03, A*11:01, A*11:02,  PYRLEKTLGKGQTGLVKLG A*24:02, A*24:10, A*33:03,  VHCVTCQKVAIKIVNREKLS B*40:01, C*03:02, C*03:04,  ESVLMKVEREIAILKLIEHPH C*14:02 VLKLHDVYENKKYLYLVLEH VSGGELFDYLVKKGRLTPK EARKFFRQIISALDFCHSHSI CHRDLKPENLLLDEKNNIRI ADFGMASLQVGDSLLETSC GSPHYACPEVIRGEKYDGR KADVWSCGVILFALLVGAL PFDDDNLRQLLEKVKRGVF HMPHFIPPDCQSLLRGMIE VDAARRLTLEHIQKHIWYI GGKNEPEPEQPIPRKVQIR SLPSLEDIDPDVLDSMHSL GCFRDRNKLLQDLLSEEEN QEKMIYFLLLDRKERYPSQE DEDLPPRNEIDPPRKRVDS PMLNRHGKRRPERKSMEV LSVTDGGSPVPARRAIEMA QHGQSKAMFSKSLDIAEA HPQFSKEDRSRSISGASSGL STSPLSSPRVTPHPSPRGSP LPTPKGTPVHTPKESPAGT PNPTPPSSPSVGGVPWRA RLNSIKNSFLGSPRFHRRKL QVPTPEEMSNLTPESSPEL AKKSWFGNFISLEKEEQIFV VIKDKPLSSIKADIVHAFLSI PSLSHSVISQTSFRAEYKAT GGPAVFQKPVKFQVDITYT EGGEAQKENGIYSVTFTLLS GPSRRFKRVVETIQAQLLST HDPPAAQHLSEPPPPAPGL SWGAGLKGQKVATSYESSL SEQ ID NO: 1926 ENSG00000177380.9 MMCEVMPTISEDGRRGSA A*02:03, A*11:01, A*11:02,  LGPDEAGGELERLMVTML A*24:10, A*33:03, B*15:01,  TERERLLETLREAQDGLAT B*39:01, B*40:01, B*58:01,  AQLRLRELGHEKDSLQRQL C*03:02, C*03:04, C*03:67,  SIALPQEFAALTKELNLCRE C*12:02 QLLEREEEIAELKAERNNTR LLLEHLECLVSRHERSLRMT VVKRQAQSPGGVSSEVEV LKALKSLFEHHKALDEKVRE RLRMALERVAVLEEELELS NQETLNLREQLSRRRSGLE EPGKDGDGQTLANGLGPG GDSNRRTAELEEALERQRA EVCQLRERLAVLCRQMSQ LEEELGTAHRELGKAEEAN SKLQRDLKEALAQREDME ERITTLEKRYLSAQREATSL HDANDKLENELASKESLYR QSEEKSRQLAEWLDDAKQ KLQQTLQKAETLPEIEAQLA QRVAALNKAEERHGNFEE RLRQLEAQLEEKNQELQRA RQREKMNDDHNKRLSETV DKLLSESNERLQLHLKERM GALEEKNSLSEEIANMKKL QDELLLNKEQLLAEMERM QMEIDQLRGRPPSSYSRSL PGSALELRYSQAPTLPSGA HLDPYVAGSGRAGKRGR WSGVKEEPSKDWERSAPA GSIPPPFPGELDGSDEEEAE GMFGAELLSPSGQADVQT LAIMLQEQLEAINKEIKLIQE EKETTEQRAEELESRVSSSG LDSLGRYRSSCSLPPSLTTST LASPSPPSSGHSTPRLAPPS PAREGTDKANHVPKEEAG APRGEGPAIPGDTPPPTPR SARLERMTQALALQAGSLE DGGPPRGSEGTPDSLHKA PKKKSIKSSIGRLFGKKEKG RMGPPGRDSSSLAGTPSD ETLATDPLGLAKLTGPGDK DRRNKRKHELLEEACRQGL PFAAWDGPTVVSWLELW VGMPAWYVAACRANVKS GAIMANLSDTEIQREIGISN PLHRLKLRLAIQEMVSLTSP SAPASSRTSTGNVWMTHE EMESLTATTKPILAYGDMN HEWVGNDWLPSLGLPQY RSYFMESLVDARMLDHLN KKELRGQLKMVDSFHRVSL HYGIMCLKRLNYDRKDLER RREESQTQIRDVMVWSNE RVMGWVSGLGLKEFATNL TESGVHGALLALDETFDYS DLALLLQIPTQNAQARQLL EKEFSNLISLGTDRRLDEDS AKSFSRSPSWRKMFREKDL RGVTPDSAEMLPPNFRSA AAGALGSPGLPLRKLQPEG QTSGSSRADGVSVRTYSC SEQ ID NO: 1927 ENSG00000177455.7 MPPPRLLFFLLFLTPMEVR A*02:03, A*11:01, A*11:02,  PEEPLVVKVEEGDNAVLQC A*24:10, B*39:01, B*40:01,  LKGTSDGPTQQLTWSRES B*58:01, C*03:02, C*03:04,  PLKPFLKLSLGLPGLGIHMR C*12:02, C*14:02, C*15:02 PLAIWLFIFNVSQQMGGFY LCQPGPPSEKAWQPGWT VNVEGSGELFRWNVSDLG GLGCGLKNRSSEGPSSPSG KLMSPKLYVWAKDRPEIW EGEPPCLPPRDSLNQSLSQ DLTMAPGSTLWLSCGVPP DSVSRGPLSWTHVHPKGP KSLLSLELKDDRPARDMW VMETGLLLPRATAQDAGK YYCHRGNLTMSFHLEITAR PVLWHWLLRTGGWKVSA VTLAYLIFCLCSLVGILHLQR ALVLRRKRKRMTDPTRRFF KVTPPPGSGPQNQYGNVL SLPTPTSGLGRAQRWAAG LGGTAPSYGNPSSDVQAD GALGSRSPPGVGPEEEEGE GYEEPDSEEDSEFYENDSN LGQDQLSQDGSGYENPED EPLGPEDEDSFSNAESYEN EDEELTQPVARTMDFLSPH GSAWDPSREATSLGSQSYE DMRGILYAAPQLRSIRGQP GPNHEEDADSYENMDNP DGPDPAWGGGGRMGTW STR SEQ ID NO: 1928 ENSG00000178209.10 MVAGMLMPRDQLRAIYE A*02:03, A*11:01, A*11:02,  VLFREGVMVAKKDRRPRSL A*24:02, A*24:10, A*33:03,  HPHVPGVTNLQVMRAMA A*34:01, B*55:02, C*03:02,  SLRARGLVRETFAWCHFY C*03:04 WYLTNEGIAHLRQYLHLPP EIVPASLQRVRRPVAMVM PARRTPHVQAVQGPLGSP PKRGPLPTEEQRVYRRKEL EEVSPETPVVPATTQRTLA RPGPEPAPAT SEQ ID NO: 1929 ENSG00000181035.9 MGNGVKEGPVRLHEDAE A*02:03, A*11:01, A*11:02,  AVLSSSVSSKRDHRQVLSSL A*24:02, A*24:07, A*24:10,  LSGALAGALAKTAVAPLDR A*33:03, B*15:01, B*39:01,  TKIIFQVSSKRFSAKEAFRVL B*40:01, C*03:02, C*03:04,  YYTYLNEGFLSLWRGNSAT C*03:67, C*12:02, C*14:02 MVRVVPYAAIQFSAHEEYK RILGSYYGFRGEALPPWPR LFAGALAGTTAASLTYPLDL VRARMAVTPKEMYSNIFH VFIRISREEGLKTLYHGFMP TVLGVIPYAGLSFFTYETLKS LHREYSGRRQPYPFERMIF GACAGLIGQSASYPLDVVR RRMQTAGVTGYPRASIAR TLRTIVREEGAVRGLYKGLS MNWVKGPIAVGISFTTFDL MQILLRHLQS SEQ ID NO: 1930 ENSG00000185404.12 MAGGGSDLSTRGLNGGVS A*02:03, A*24:10, A*33:03,  QVANEMNHLPAHSQSLQ C*03:02 RLFTEDQDVDEGLVYDTVF KHFKRHKLEISNAIKKTFPFL EGLRDRELITNK SEQ ID NO: 1931 ENSG00000185686.13 MERRRLWGSIQSRYISMS A*02:03, A*11:01, A*11:02,  VWTSPRRLVELAGQSLLKD A*24:10, A*33:03, B*15:01,  EALAIAALELLPRELFPPLF B*39:01, B*40:01, B*58:01,  MAAFDGRHSQTLKAMVQ C*03:02, C*03:04, C*14:02 AWPFTCLPLGVLMKGQHL HLETFKAVLDGLDVLLAQE VRPRRWKLQVLDLRKNSH QDFWTVWSGNRASLYSFP EPEAAQPMTKKRKVDGLS TEAEQPFIPVEVLVDLFLKE GACDELFSYLIEKVKRKKNV LRLCCKKLKIFAMPMQDIK MILKMVQLDSIEDLEVTCT WKLPTLAKFSPYLGQMINL RRLLLSHIHASSYISPEKEEQ YIAQFTSQFLSLQCLQALYV DSLFFLRGRLDQLLRHVMN PLETLSITNCRLSEGDVMHL SQSPSVSQLSVLSLSGVML TDVSPEPLQALLERASATL QDLVFDECGITDDQLLALL PSLSHCSQLTTLSFYGNSISI SALQSLLQHLIGLSNLTHVL YPVPLESYEDIHGTLHLERL AYLHARLRELLCELGRPSM VWLSANPCPHCGDRTFYD PEPILCPCFMPN SEQ ID NO: 1932 ENSG00000185989.9 MAVEDEGLRVFQSVKIKIG A*02:03, A*11:01, A*11:02,  EAKNLPSYPGPSKMRDCYC A*24:02, A*24:07, A*24:10,  TVNLDQEEVFRTKIVEKSLC A*33:03, B*15:01, B*15:27,  PFYGEDFYCEIPRSFRHLSF B*39:01, B*40:01, B*58:01,  YIFDRDVFRRDSIIGKVAIQ C*03:02, C*03:04, C*07:02,  KEDLQKYHNRDTWFQLQH C*12:02, C*14:02 VDADSEVQGKVHLELRLSE VITDTGVVCHKLATRIVEC QGLPIVNGQCDPYATVTLA GPFRSEAKKTKVKRKTNNP QFDEVFYFEVTRPCSYSKKS HFDFEEEDVDKLEIRVDLW NASNLKFGDEFLGELRIPLK VLRQSSSYEAWYFLQPRD NGSKSLKPDDLGSLRLNVV YTEDHVFSSDYYSPLRDLLL KSADVEPVSASAAHILGEV CREKQEAAVPLVRLFLHYG RVVPFISAIASAEVKRTQDP NTIFRGNSLASKCIDETMKL AGMHYLHVTLKPAIEEICQ SHKPCEIDPVKLKDGENLE NNMENLRQYVDRVFHAIT ESGVSCPTVMCDIFFSLREA AAKRFQDDPDVRYTAVSSF IFLRFFAPAILSPNLFQLTPH HTDPQTSRTLTLISKTVQTL GSLSKSKSASFKESYMATFY EFFNEQKYADAVKNFLDLIS SSGRRDPKSVEQPIVLKEG SEQ ID NO: 1933 ENSG00000196961.8 MPAVSKGDGMRGLAVFIS A*02:03, A*11:01, A*11:02,  DIRNCKSKEAEIKRINKELA A*24:02, A*24:07, A*24:10,  NIRSKFKGDKALDGYSKKK A*33:03, A*34:01, B*15:01,  YVCKLLFIFLLGHDIDFGHM B*15:27, B*39:01, B*40:01,  EAVNLLSSNKYTEKQIGYLFI B*40:06, B*58:01, C*03:02,  SVLVNSNSELIRLINNAIKN C*03:04, C*03:67, C*08:01,  DLASRNPTFMCLALHCIAN C*12:02, C*14:02, C*15:02 VGSREMGEAFAADIPRILV AGDSMDSVKQSAALCLLRL YKASPDLVPMGEWTARVV HLLNDQHMGVVTAAVSLI TCLCKKNPDDFKTCVSLAV SRLSRIVSSASTDLQDYTYY FVPAPWLSVKLLRLLQCYP PPEDAAVKGRLVECLETVL NKAQEPPKSKKVQHSNAK NAILFETISLIIHYDSEPNLLV RACNQLGQFLQHRETNLR YLALESMCTLASSEFSHEAV KTHIDTVINALKTERDVSVR QRAADLLYAMCDRSNAKQ IVSEMLRYLETADYAIREEIV LKVAILAEKYAVDYSWYVD TILNLIRIAGDYVSEEVWYR VLQIVTNRDDVQGYAAKT VFEALQAPACHENMVKVG GYILGEFGNLIAGDPRSSPP VQFSLLHSKFHLCSVATRAL LLSTYIKFINLFPETKATIQG VLRAGSQLRNADVELQQR AVEYLTLSSVASTDVLATVL EEMPPFPERESSILAKLKRK KGPGAGSALDDGRRDPSS NDINGGMEPTPSTVSTPSP SADLLGLRAAPPPAAPPAS AGAGNLLVDVFDGPAAQP SLGPTPEEAFLSPGPEDIGP PIPEADELLNKFVCKNNGV LFENQLLQIGVKSEFRQNL GRMYLFYGNKTSVQFQNF SPTVVHPGDLQTQLAVQT KRVAAQVDGGAQVQQVL NIECLRDFLTPPLLSVRFRY GGAPQALTLKLPVTINKFF QPTEMAAQDFFQRWKQL SLPQQEAQKIFKANHPMD AEVTKAKLLGFGSALLDNV DPNPENFVGAGIIQTKALQ VGCLLRLEPNAQAQMYRL TLRTSKEPVSRHLCELLAQQ F SEQ ID NO: 1934 ENSG00000197530.8 MAGALRRGRALGSRPSGP A*02:03, A*11:01, A*11:02,  TVSSRRSPQCPVAQEGLGA A*24:02, A*24:07, A*24:10,  RSRPRVAPRSLARCGPSSRL A*33:03, B*15:01, B*39:01,  MGWKPSEARGQSQSFQA B*40:01, B*58:01, C*03:02,  SGLQPRSLKAARRATGRPD C*03:04, C*07:02, C*12:02,  RSRAAPPNMDPDPQAGV C*14:02 QVGMRVVRGVDWKWGQ QDGGEGGVGTVVELGRH GSPSTPDRTVVVQWDQG TRTNYRAGYQGAHDLLLYD NAQIGVRHPNIICDCCKKH GLRGMRWKCRVCLDYDLC TQCYMHNKHELAHAFDRY ETAHSRPVTLSPRQGLPRIP LRGIFQGAKVVRGPDWE WGSQDGGEGKPGRVVDI RGWDVETGRSVASVTWA DGTTNVYRVGHKGKVDLK CVGEAAGGFYYKDHLPRLG KPAELQRRVSADSQPFQH GDKVKCLLDTDVLREMQE GHGGWNPRMAEFIGQTG TVHRITDRGDVRVQFNHE TRWTFHPGALTKHHSFWV GDVVRVIGDLDTVKRLQA GHGEWTDDMAPALGRVG KVVKVFGDGNLRVAVAGQ RWTFSPSCLVAYRPEEDAN LDVAERARENKSSLSVALD KLRAQKSDPEHPGRLVVEV ALGNAARALDLLRRRPEQV DTKNQGRTALQVAAYLGQ VELIRLLLQARAGVDLPDDE GNTALHYAALGNQPEATR VLLSAGCRADAINSTQSTA LHVAVQRGFLEVVRALCER GCDVNLPDAHSDTPLHSAI SAGTGASGIVEVLTEVPNID VTATNSQGFTLLHHASLKG HALAVRKILARARQLVDAK KEDGFTALHLAALNNHREV AQILIREGRCDVNVRNRKL QSPLHLAVQQAHVGLVPLL VDAGCSVNAEDEEGDTAL HVALQRHQLLPLVADGAG GDPGPLQLLSRLQASGLPG SAELTVGAAVACFLALEGA DVSYTNHRGRSPLDLAAEG RVLKALQGCAQRFRERQA GGGAAPGPRQTLGTPNTV TNLHVGAAPGPEAAECLV CSELALLVLFSPCQHRTVCE ECARRMKKCIRCQVVVSKK LRPDGSEVASAAPAPGPPR QLVEELQSRYRQMEERITC PICIDSHIRLVFQCGHGACA PCGSALSACPICRQPIRDRI QIFV SEQ ID NO: 1935 ENSG00000204839.4 MAGGVWGRSRAREAPVG A*02:03, A*11:01, A*11:02,  ALTLTALTEGIRARQGQPQ A*24:02, A*24:07, A*24:10,  GPPSAGPQPKSWEVKPEA A*33:03, B*39:01, B*40:01,  EPQTQALTAPSEAEPGRGA B*58:01, C*03:02, C*03:04,  TVPEAGSEPCSLNSALEPAP C*14:02 EGPHQVPQSSWEEGVLAD LALYTAACLEEAGFAGTQA TVLTLSSALEARGERLEDQV HALVRGLLAQVPSLAEGRP WRAALRVLSALALEHARD VVCALLPRSLPADRVAAEL WRSLSRNQRVNGQVLVQL LWALKGASGPEPQALAAT RALGEMLAVSGCVGATRG FYPHLLLALVTQLHKLARSP CSPDMPKIWVLSHRGPPH SHASCAVEALKALLTGDGG RMVVTCMEQAGGWRRLV GAHTHLEGVLLLASAMVA HADHHLRGLFADLLPRLRS ADDPQRLTAMAFFTGLLQ SRPTARLLREEVILERLLTW QGDPEPTVRWLGLLGLGH LALNRRKVRHVSTLLPALLG ALGEGDARLVGAALGALR RLLLRPRAPVRLLSAELGPR LPPLLDDTRDSIRASAVGLL GTLVRRGRGGLRLGLRGPL RKLVLQSLVPLLLRLHDPSR DAAESSEWTLARCDHAFC WGLLEELVTVAHYDSPEAL SHLCCRLVQRYPGHVPNFL SQTQGYLRSPQDPLRRAA AVLIGFLVHHASPGCVNQD LLDSLFQDLGRLQSDPKPA VAAAAHVSAQQVA SEQ ID NO: 1936 ENSG00000205277.5 MLVIWILTLALRLCASVTTV A*02:03, A*11:01, A*11:02,  TPGSTVNTSIGGNTTSASTP A*24:02, A*24:10, A*33:03,  SSSDPFTTFSDYGVSVTFIT B*15:01, B*39:01, B*40:01,  GSTATKHFLDSSTNSGHSE B*55:02, B*58:01, C*03:02,  ESTVSHSGPGATGTTLFPS C*03:04, C*03:67, C*07:02,  HSATSVFVGEPKTSPITSAS C*12:02, C*14:02, C*15:02 METTALPGSTTTAGLSEKS TTFYSSPRSPDRTLSPARTT SSGVSEKSTTSHSRPGPTHT IAFPDSTTMPGVSQESTAS HSIPGSTDTTLSPGTTTPSSL GPESTTFHSSPGYTKTTRLP DNTTTSGLLEASTPVHSST GSPHTTLSPSSSTTHEGEPT TFQSWPSSKDTSPAPSGTT SAFVKLSTTYHSSPSSTPTT HFSASSTTLGHSEESTPVHS SPVATATTPPPARSATSGH VEESTAYHRSPGSTQTMHF PESSTTSGHSEESATFHGST THTKSSTPSTTAALAHTSYH SSLGSTETTHFRDSSTISGRS EESKASHSSPDAMATTVLP AGSTPSVLVGDSTPSPISSG SMETTALPGSTTKPGLSEKS TTFYSSPRSPDTTHLPASM TSSGVSEESTTSHSRPGSTH TTAFPGSTTMPGLSQESTA SHSSPGPTDTTLSPGSTTAS SLGPEYTTFHSRPGSTETTL LPDNTTASGLLEASMPVHS STRSPHTTLSPAGSTTRQG ESTTFHSWPSSKDTRPAPP TTTSAFVEPSTTSHGSPSSIP TTHISARSTTSGLVEESTTY HSSPGSTQTMHFPESDTTS GRGEESTTSHSSTTHTISSA PSTTSALVEEPTSYHSSPGS TATTHFPDSSTTSGRSEEST ASHSSQDATGTIVLPARSTT SVLLGESTTSPISSGSMETT ALPGSTTTPGLSERSTTFHS SPRSPATTLSPASTTSSGVS EESTTSRSRPGSTHTTAFPD STTTPGLSRHSTTSHSSPGS TDTTLLPASTTTSGPSQEST TSHSSSGSTDTALSPGSTTA LSFGQESTTFHSNPGSTHT TLFPDSTTSSGIVEASTRVH SSTGSPRTTLSPASSTSPGL QGESTAFQTHPASTHTTPS PPSTATAPVEESTTYHRSP GSTPTTHFPASSTTSGHSEK STIFHSSPDASGTTPSSAHS TTSGRGESTTSRISPGSTEIT TLPGSTTTPGLSEASTTFYSS PRSPTTTLSPASMTSLGVG EESITSRSQPGSTHSTVSPA STTTPGLSEESTTVYSSSRG STETTVFPHSTTTSVHGEEP TTFHSRPASTHTTLFTEDST TSGLTEESTAFPGSPASTQT GLPATLTTADLGEESTTFPS SSGSTGTKLSPARSTTSGLV GESTPSRLSPSSTETTTLPGS PTTPSLSEKSTTFYTSPRSPD ATLSPATTTSSGVSEESSTS HSQPGSTHTTAFPDSTTTS DLSQEPTTSHSSQGSTEATL SPGSTTASSLGQQSTTFHSS PGDTETTLLPDDTITSGLVE ASTPTHSSTGSLHTTLTPAS STSAGLQEESTTFQSWPSS SDTTPSPPGTTAAPVEVST TYHSRPSSTPTTHFSASSTT LGRSEESTTVHSSPGATGT ALFPTRSATSVLVGEPTTSP ISSGSTETTALPGSTTTAGLS EKSTTFYSSPRSPDTTLSPAS TTSSGVSEESTTSHSRPGST HTTAFPGSTTMPGVSQEST ASHSSPGSTDTTLSPGSTTA SSLGPESITFHSSPGSTETT LLPDNTTASGLLEASTPVHS STGSPHTTLSPAGSTTRQG ESTTFQSWPSSKDTMPAP PTTTSAFVELSTTSHGSPSS TPTTHFSASSTTLGRSEEST TVHSSPVATATTPSPARSTT SGLVEESTAYHSSPGSTQT MHFPESSTASGRSEESRTS HSSTTHTISSPPSTTSALVEE PTSYHSSPGSTATTHFPDSS TTSGRSEESTASHSSQDAT GTIVLPARSTTSVLLGESTTS PISSGSMETTALPGSTTTPG LSEKSTTFHSSPRSPATTLSP ASTTSSGVSEESTTSHSRPG STHTTAFPDSTTTPGLSRHS TTSHSSPGSTDTTLLPASTT TSGPSQESTTSHSSPGSTDT ALSPGSTTALSFGQESTTFH SSPGSTHTTLFPDSTTSSGI VEASTRVHSSTGSPRTTLSP ASSTSPGLQGESTAFQTHP ASTHTTPSPPSTATAPVEES TTYHRSPGSTPTTHFPASST TSGHSEKSTIFHSSPDASGT TPSSAHSTTSGRGESTTSRI SPGSTEITTLPGSTTTPGLSE ASTTFYSSPRSPTTTLSPAS MTSLGVGEESTTSRSQPGS THSTVSPASTTTPGLSEEST TVYSSSPGSTETTVFPRTPT TSVRGEEPTTFHSRPASTH TTLFTEDSTTSGLTEESTAFP GSPASTQTGLPATLTTADL GEESTTFPSSSGSTGTTLSP ARSTTSGLVGESTPSRLSPS STETTTLPGSPTTPSLSEKST TFYTSPRSPDATLSPATTTS SGVSEESSTSHSQPGSTHT TAFPDSTTTPGLSRHSTTSH SSPGSTDTTLLPASTTTSGP SQESTTSHSSPGSTDTALSP GSTTALSFGQESTTFHSSPG STHTTLFPDSTTSSGIVEAST RVHSSTGSPRTTLSPASSTS PGLQGESTTFQTHPASTHT TPSPPSTATAPVEESTTYHR SPGSTPTTHFPASSTTSGHS EKSTIFHSSPDASGTTPSSA HSTTSGRGESTTSRISPGST EITTLPGSTTTPGLSEASTTF YSSPRSPTTTLSPASMTSLG VGEESTTSRSQPGSTHSTV SPASTTTPGLSEESTTVYSSS PGSTETTVFPRSTTTSVRGE EPTTFHSRPASTHTTLFTED STTSGLTEESTAFPGSPAST QTGLPATLTTADLGEESTTE PSSSGSTGTTLSPARSTTSG LVGESTPSRLSPSSTETTTLP GSPTTPSLSEKSTTFYTSPRS PDATLSPATTTSSGVSEESS TSHSQPGSTHTTAFPDSTT TSGLSQEPTASHSSQGSTE ATLSPGSTTASSLGQQSTTF HSSPGDTETTLLPDDTITSG LVEASTPTHSSTGSLHTTLT PASSTSAGLQEESTTFQSW PSSSDTTPSPPGTTAAPVE VSTTYHSRPSSTPTTHFSAS STTLGRSEESTTVHSSPGAT GTALFPTRSATSVLVGEPTT SPISSGSTETTALPGSTTTA GLSEKSTTFYSSPRSPDTTLS PASTTSSGVSEESTTSHSRP GSTHTTAFPGSTTMPGVS QESTASHSSPGSTDTTLSP GSTTASSLGPESTTFHSGPG STETTLLPDNTTASGLLEAS TPVHSSTGSPHTTLSPAGST TRQGESTTFQSWPNSKDT TPAPPTTTSAFVELSTTSHG SPSSTPTTHFSASSTTLGRS EESTTVHSSPVATATTPSPA RSTTSGLVEESTTYHSSPGS TQTMHFPESDTTSGRGEES TTSHSSTTHTISSAPSTTSAL VEEPTSYHSSPGSTATTHFP DSSTTSGRSEESTASHSSQ DATGTIVLPARSTTSVLLGE STTSPISSGSMETTALPGST TTPGLSEKSTTFHSSPRSPA TTLSPASTTSSGVSEESTTS HSRPGSTHTTAFPDSTTTP GLSRHSTTSHSSPGSTDTTL LPASTTTSGSSQESTTSHSS SGSTDTALSPGSTTALSFG QESTTFHSSPGSTHTTLFPD STTSSGIVEASTRVHSSTGS PRTTLSPASSTSPGLQGEST AFQTHPASTHTTPSPPSTA TAPVEESTTYHRSPGSTPTT HFPASSTTSGHSEKSTIFHS SPDASGTTPSSAHSTTSGR GESTTSRISPGSTEITTLPGS TTTPGLSEASTTFYSSPRSP TTTLSPASMTSLGVGEESTT SRSQPGSTHSTVSPASTTTP GLSEESTTVYSSSPGSTETT VFPRSTTTSVRREEPTTFHS RPASTHTTLFTEDSTTSGLT EESTAFPGSPASTQTGLPA TLTTADLGEESTTFPSSSGS TGTKLSPARSTTSGLVGEST PSRLSPSSTETTTLPGSPQP SLSEKSTTFYTSPRSPDATLS PATTTSSGVSEESSTSHSQP GSTHTTAFPDSTTTSGLSQ EPTTSHSSQGSTEATLSPGS TTASSLGQQSTTFHSSPGD TETTLLPDDTITSGLVEASTP THSSTGSLHTTLTPASSTST GLQEESTTFQSWPSSSDTT PSPPSTTAVPVEVSTTYHSR PSSTPTTHFSASSTTLGRSE ESTTVHSSPGATGTALFPTR SATSVLVGEPTTSPISSGSTE TTALPGSTTTAGLSEKSTTF YSSPRSPDTTLSPASTTSSG VSEESTTSHSRPGSMHTTA FPSSTTMPGVSQESTASHS SPGSTDTTLSPGSTTASSLG PESTTEHSSPGSTETTLLPD NTTASGLLEASTPVHSSTGS PHTTLSPAGSTTRQGESTT FQSWPNSKDTTPAPPTTTS AFVELSTTSHGSPSSTPTTH FSASSTTLGRSEESTTVHSS PVATATTPSPARSTTSGLVE ESTTYHSSPGSTQTMHFPE SNTTSGRGEESTTSHSSTTH TISSAPSTTSALVEEPTSYHS SPGSTATTHFPDSSTTSGRS EESTASHSSQDATGTIVLPA RSTTSVLLGESTTSPISSGS METTALPGSTTTPGLSEKST TFHSSPSSTPTTHFSASSTTL GRSEESTTVHSSPVATATTP SPARSTTSGLVEESTAYHSS PGSTQTMHFPESSTASGRS EESRTSHSSTTHTISSPPSTT SALVEEPTSYHSSPGSIATT HFPESSTTSGRSEESTASHS SPDTNGITPLPAHFTTSGRI AESTTFYISPGSMETTLAST ATTPGLSAKSTILYSSSRSPD QTLSPASMTSSSISGEPTSL YSQAESTHTTAFPASTTTSG LSQESTTFHSKPGSTETTLS PGSITTSSFAQEFTTPHSQP GSALSTVSPASTTVPGLSEE STTFYSSPGSTETTAFSHSN TMSIHSQQSTPFPDSPGFT HTVLPATLTTTDIGQESTAF HSSSDATGTTPLPARSTAS DLVGEPTTFYISPSPTYTTLF PASSSTSGLTEESTTFHTSPS FTSTIVSTESLETLAPGLCQE GQIWNGKQCVCPQGYVG YQCLSPLESFPVETPEKLNA TLGMTVKVTYRNFTEKMN DASSQEYQNFSTLFKNRM DVVLKGDNLPQYRGVNIR RLLNGSIVVKNDVILEADYT LEVEELFENLAEIVKAKIMN ETRTTLLDPDSCRKAILCYSE EDTFVDSSVTPGFDFQEQC TQKAAEGYTQFYYVDVLD GKLACVNKCTKGTKSQMN CNLGTCQLQRSGPRCLCPN TNTHWYWGETCEFNIAKS LVYGIVGAVMAVLLLALIILI ILFSLSQRKRHREQYDVPQ EWRKEGTPGIFQKTAIWE DQNLRESRFGLENAYNNF RPTLETVDSGTELHIQRPE MVASTV SEQ ID NO: 1937 ENSG00000205744.5 MESRAEGGSPAVFDWFFE A*02:03, A*11:01, A*11:02,  AACPASLQEDPPILRQFPP A*24:10, A*33:03, B*15:01,  DFRDQEAMQMVPKFCFP B*39:01, B*40:01, B*55:02,  FDVEREPPSPAVQHFTFAL B*58:01, C*03:02, C*03:04,  TDLAGNRRFGFCRLRAGT C*14:02 QSCLCILSHLPWFEVFYKLL NTVGDLLAQDQVTEAEELL QNLFQQSLSGPQASVGLEL GSGVTVSSGQGIPPPTRGN SKPLSCFVAPDSGRLPSIPE NRNLTELVVAVTDENIVGL FAALLAERRVLLTASKLSTLT SCVHASCALLYPMRWEHV LIPTLPPHLLDYCCAPMPYL IGVHASLAERVREKALEDV VVLNVDANTLETTFNDVQ ALPPDVVSLLRLRLRKVALA PGEGVSRLFLKAQALLFGG YRDALVCSPGQPVTFSEEV FLAQKPGAPLQAFHRRAV HLQLFKQFIEARLEKLNKGE GFSDQFEQEITGCGASSGA LRSYQLWADNLKKGGGAL LHSVKAKTQPAVKNMYRS AKSGLKGVQSLLMYKDGD SVLQRGGSLRAPALPSRSD RLQQRLPITQHFGKNRPLR PSRRRQLEEGTSEPPGAGT PPLSPEDEGCPWAEEALDS SFLGSGEELDLLSEILDSLSM GAKSAGSLRPSQSLDCCHR GDLDSCFSLPNIPRWQPD DKKLPEPEPQPLSLPSLQN ASSLDATSSSKDSRSQLIPS ESDQEVTSPSQSSTASADP SIWGDPKPSPLTEPLILHLT PSHKAAEDSTAQENPTPW LSTAPTEPSPPESPQILAPTK PNFDIAWTSQPLDPSSDPS SLEDPRARPPKALLAERAHL QPREEPGALNSPATPTSNC QKSQPSSRPRVADLKKCFE G SEQ ID NO: 1938 ENSG00000213420.3 MSALRPLLLLLLPLCPGPGP A*02:03, A*11:01, A*11:02,  GPGSEAKVTRSCAETRQVL A*24:02, A*24:10, A*33:03,  GARGYSLNLIPPALISGEHL B*15:01, B*15:27, B*38:02,  RVCPQEYTCCSSETEQRLIR B*39:01, B*40:01, B*58:01,  ETEATFRGLVEDSGSFLVHT C*03:02, C*03:04, C*12:02,  LAARHRKFDEFFLEMLSVA C*14:02, C*15:02 QHSLTQLFSHSYGRLYAQH ALIFNGLFSRLRDFYGESGE GLDDTLADFWAQLLERVF PLLHPQYSFPPDYLLCLSRL ASSTDGSLQPFGDSPRRLR LQITRTLVAARAFVQGLET GRNVVSEALKVPVSEGCSQ ALMRLIGCPLCRGVPSLMP CQGFCLNVVRGCLSSRGLE PDWGNYLDGLLILADKLQ GPFSFELTAESIGVKISEGL MYLQENSAKVSAQVFQEC GPPDPVPARNRRAPPPRE EAGRLWSMVTEEERPTTA AGTNLHRLVWELRERLAR MRGFWARLSLTVCGDSR MAADASLEAAPCWTGAG RGRYLPPVVGGSPAEQVN NPELKVDASGPDVPTRRRR LQLRAATARMKTAALGHD LDGQDADEDASGSGGGQ QYADDWMAGAVAPPARP PRPPYPPRRDGSGGKGGG GSARYNQGRSRSGGASIGF HTQTILILSLSALALLGPR SEQ ID NO: 1939 ENSG00000225485.3 MNGVAFCLVGIPPRPEPRP A*02:03, A*11:01, A*11:02,  PQLPLGPRDGCSPRRPFP A*24:02, A*24:07, A*24:10,  WQGPRTLLLYKSPQDGFG B*15:01, B*39:01, B*40:01,  FTLRHFIVYPPESAVHCSLK B*55:02, B*58:01, C*03:02,  EEENGGRGGGPSPRYRLEP C*03:04, C*03:67, C*12:02,  MDTIFVKNVKEDGPAHRA C*14:02, C*15:02 GLRTGDRLVKVNGESVIGK TYSQVIALIQNSDDTLELSI MPKDEDILQLAYSQDAYLK GNEPYSGEARSIPEPPPICY PRKTYAPPARASTRATMVP EPTSALPSDPRSPAAWSDP GLRVPPAARAHLDNSSLG MSQPRPSPGAFPHLSSEPR TPRAFPEPGSRVPPSRLEC QQALSHWLSNQVPRRAG ERRCPAMAPRARSASQDR LEEVAAPRPWPCSTSQDAL SQLGQEGWHRARSDDYLS RATRSAEALGPGALVSPRF ERCGWASQRSSARTPACP TRDLPGPQAPPPSGLQGL DDLGYIGYRSYSPSFQRRT GLLHALSFRDSPFGGLPTF NLAQSPASFPPEASEPPRV VRPEPSTRALEPPAEDRGD EVVLRQKPPTGRKVQLTPA RQMNLGFGDESPEPEASG RGERLGRKVAPLATTEDSL ASIPFIDEPTSPSIDLQAKHV PASAVVSSAMNSAPVLGT SPSSPTFTFTLGRHYSQDCS SIKAGRRSSYLLAITTERSKS CDDGLNTFRDEGRVLRRLP NRIPSLRMLRSFFTDGSLDS WGTSEDADAPSKRHSTSD LSDATFSDIRREGWLYYKQI LTKKGKKAGSGLRQWKRV YAALRARSLSLSKERREPGP AAAGAAAAGAGEDEAAPV CIG SEQ ID NO: 1940 ENSG00000243449.2 MFRAALEDSVEKKSSLKET A*02:03, A*24:10, A*33:03,  ETTSKGTSKYDRERETEMK B*27:04, B*38:02, B*39:01,  TVMGMKMHFWVRTPAS B*40:01, C*01:02, C*03:02,  GRGRGGSDHARSRAAPLP C*03:04, C*03:67, C*04:01,  LLA C*07:02, C*14:02, C*15:02 SEQ ID NO: 1941 ENSG00000261787.1 MDRGRPAGSPLSASAEPA A*02:03, A*24:02, A*24:10,  PLAAAIRDSRPGRTGPGPA A*33:03, B*40:01, C*03:02,  GPGGGSRSGSGRPAAANA C*03:04, C*12:02, C*14:02 ARERSRVQTLRHAFLELQR TLPSVPPDTKLSKLDVLLLA TTYIAHLTRSLQDDAEAPA DAGLGALRGDGYLHPVKK WPMRSRLYIGATGQFLKH SVSGEKTNHDNTPTDSQP

TABLE 10 Peptide pools for alternative promoters Peptide Alternative Corresponding SEQ ID NO. Pool Promoter Peptide Sequence HLA variant SEQ ID NO: 1 DNAH3 MAEKLQEANFLLEDI A*02:01 1942 SEQ ID NO. QYSHIADKVSEVPAN A*02:03 1943 SEQ ID NO: FLKKSSAVTVKLRR A*03:01 1944 SEQ ID NO: PKLKYIPLKFSFTAA A*24:02 1945 SEQ ID NO: EHLHTVNPMMLRLKE A*33:03 1946 SEQ ID NO: VSDFLIQTFKVFQKN B*15:01 1947 SEQ ID NO: DNTAEQNIAAFLKEN B*40:01 1948 SEQ ID NO: VNPMMLRLKELWFAE B*58:01 1949 SEQ ID NO: KTSLTFPGSRPMSPE C*03:02 1950 SEQ ID NO: IEEYFASVASFMSLQ C*14:02 1951 SEQ ID NO: NEIASMNITVPLAMF C*15:02 1952 SEQ ID NO: 2 DST NPKLTLGLIWTIILH A*02:01 1953 SEQ ID NO: FTKWINQHLMKVRKH A*02:03 1954 SEQ ID NO: ERDKVQKKTFTKWIN A*03:01 1955 SEQ ID NO: ISLLEVLSGDTLPRE B*40:01 1956 SEQ ID NO: MAGYLSPAAYLYVEE C*03:02 1957 SEQ ID NO: MAGYLSPAAYLYVE C*14:02 1958 SEQ ID NO: 3 EPS8L1 ADVSQYPVNHLVTFC A*02:01 1959 SEQ ID NO: EVDILNHVFDDVESF A*02:03 1960 SEQ ID NO: MSTATGPEAAPKPSA A*11:01 1961 SEQ ID NO: AQPDVHFFQGLRLGA A*33:03 1962 SEQ ID NO: ILNHVFDDVESFVSR B*15:02 1963 SEQ ID NO: VSQYPVNHLVTFCLG B*35:03 1964 SEQ ID NO: PASKEELESYPLGAI B*40:01 1965 SEQ ID NO: EPERAQPDVHFFQGL B*58:01 1966 SEQ ID NO: 4 FRMD4B VEDLLFSGSRFVWNL A*02:01 1967 SEQ ID NO: LLDLVASHFNLKEKE A*11:01 1968 SEQ ID NO: TVSTLRRWYTERLRA A*33:03 1969 SEQ ID NO: QIEVESETIFKLAAF B*40:01 1970 SEQ ID NO: VWNLTVSTLRRWYTE B*58:01 1971 SEQ ID NO: AVRFYIESISFLKDK C*07:02 1972 SEQ ID NO: 5 LAMA3 AEGVLLDYLVLLPRD A*02:01 1973 SEQ ID NO: SRIAMYELLADADIQ A*02:03 1974 SEQ ID NO: RTNTLLGHLISKAQR A*03:01 1975 SEQ ID NO: VIHFYQAAHPTFPAQ A*24:02 1976 SEQ ID NO: TKATNIRLRFLRTNT A*33:03 1977 SEQ ID NO: YAQMTSVQNDVRITL A*68:01 1978 SEQ ID NO: CLLYQHLPVTRFPCT B*15:01 1979 SEQ ID NO: DKVSSYGGYLTYQAK B*15:02 1980 SEQ ID NO: LSGREVELHLRLRIP B*40:01 1981 SEQ ID NO: LHKKSMDKSLEFITN B*58:01 1982 SEQ ID NO: DGYFALEKSNYFGCQ C*03:02 1983 SEQ ID NO: ENNYYFPDLHHMKYE C*07:02 1984 SEQ ID NO: ILRYVNPGTEAVSGH C*12:02 1985 SEQ ID NO: ADPFSITPGIWVACI C*15:02 1986 SEQ ID NO: 6 MET QNVILHEHHIFLGAT A*02:01 1987 SEQ ID NO: CKEALAKSEMNVNMK A*02:03 1988 SEQ ID NO: MDRSAMCAFPIKYVN A*11:01 1989 SEQ ID NO: TDQVIDVLPEFRDS A*24:02 1990 SEQ ID NO: LDAQTFHTRIIRFCS A*33:03 1991 SEQ ID NO: SNNFIYFLTVQRETL A*68:01 1992 SEQ ID NO: KDGFMFLTDQAYIDV B*15:01 1993 SEQ ID NO: RDSYPIKYVHAFESN B*35:03 1994 SEQ ID NO: QKVAEYKTGPVLEHP B*40:01 1995 SEQ ID NO: CSSKANLSGGVWKDN B*58:01 1996 SEQ ID NO: RDEYRTEFTTALQRV C*07:02 1997 SEQ ID NO: TINSSYFPDHPLHSI C*12:03 1998 SEQ ID NO: PMDRSAMCAFPIKYV C*15:02 1999 SEQ ID NO: 7 MIB2 GASGIVEVLTEVPNI A*02:01 2000 SEQ ID NO: QGFTLLHHASLKGHA A*03:01 2001 SEQ ID NO: ENKSSLSVALDKLRA A*11:01 2002 SEQ ID NO: QVAAYLGQVELIRLL A*24:02 2003 SEQ ID NO: TALHLAALNNHREVA A*33:03 2004 SEQ ID NO: CVGEAAGGFYYKDHL A*68:01 2005 SEQ ID NO: LQRRVSADSQFFQHG B*15:01 2006 SEQ ID NO: GNLRVAVAGQRWTFS B*58:01 2007 SEQ ID NO: EDGFTALHLAALNNH C*03:02 2008 SEQ ID NO: GGFYYKDHLPRLGKP C*07:02 2009 SEQ ID NO: 8 MRC2 DSCYQFNFQSTLSWR A*02:01 2010 SEQ ID NO: TDGSIINFISWAPGK A*02:03 2011 SEQ ID NO: RDCSIALPYVCKKKP A*11:01 2012 SEQ ID NO: EWLRFQEAEYKFFEH A*24:02 2013 SEQ ID NO: SGDEVMYTHWNRDQP A*33:03 2014 SEQ ID NO: RFEQAFVSSLIYNWE B*15:02 2015 SEQ ID NO: GWTWHSPSCYWLGED B*38:02 2016 SEQ ID NO: TNRFEQAFVSSLIYN B*40:01 2017 SEQ ID NO: QGRREWLRFQEAEYK B*40:06 2018 SEQ ID NO: LCALPYHEVYTIQGN B*51:01 2019 SEQ ID NO: CPIKSNDCETFWDKD B*58:01 2020 SEQ ID NO: GGCVALATGSAMGLW C*03:02 2021 SEQ ID NO: EGEYFWTALQDLNST C*14:02 2022 SEQ ID NO: 9 NOS2 PDELLPQAIEFVNQY A*02:01 2023 SEQ ID NO: SKSCLGSIMTPKSLT A*11:01 2024 SEQ ID NO: VKLDATPLSSPRHVR A*68:01 2025 SEQ ID NO: IGRIQWSNLQVFDAR B*15:01 2026 SEQ ID NO: AIEFVNQYYGSFKEA B*15:02 2027 SEQ ID NO: TKEIETTGTYQLTGD B*40:01 2028 SEQ ID NO: MACPWKFLFKTK B*58:01 2029 SEQ ID NO: 10 PLEC RPRSLHPHVPGVTNL A*02:01 2030 SEQ ID NO: MVAGMLMPRDQL A*11:01 2031 SEQ ID NO: HLRQYLHLPPEIVPA A*24:02 2032 SEQ ID NO: RETFAWCHFYWYLTN C*03:02 2033 SEQ ID NO: 11 PLEKHG5 KKKSLGEVLLPVFER A*02:01 2034 SEQ ID NO: LWASVMAPVLEKARR A*03:01 2035 SEQ ID NO: LHTEASYIRKLRVII A*33:03 2036 SEQ ID NO: SLGEVLLPVFERKGI A*68:01 2037 SEQ ID NO: WKNRAASRFSGFFSS B*15:01 2038 SEQ ID NO: KNMSEFLGEASIPGQ B*40:01 2039 SEQ ID NO: GSSGSTNTGDSWKNR B*58:01 2040 SEQ ID NO: TFEAYRFGGHYLRVK C*14:02 2041 SEQ ID NO: 12 PTGDS THHTLWMGLALLGVL A*02:01 2042 SEQ ID NO: HTLWMGLALLGVLGD A*02:03 2043 SEQ ID NO: APEAQVSVQPNFQQD B*15:01 2044 SEQ ID NO: MATHHTLWMGLA C*03:02 2045 SEQ ID NO: 13 RASA3 GPSKMRDCYCTVNLD A*02:03 2046 SEQ ID NO: EIPRSFRHLSFYIFD A*03:01 2047 SEQ ID NO: RYTAVSSFIFLRFFA A*11:01 2048 SEQ ID NO: FKESYMATFYEFFNE A*24:02 2049 SEQ ID NO: LSFYIFDRDVFRRDS A*33:03 2050 SEQ ID NO: KESYMATFYEFFNEQ B*15:01 2051 SEQ ID NO: DADSEVQGKVHLELR B*40:01 2052 SEQ ID NO: DVRYTAVSSFIFLRF B*58:01 2053 SEQ ID NO: DHVFSSDYYSPLRDL C*03:02 2054 SEQ ID NO: GEDFYCEIPRSFRHL C*07:02 2055 SEQ ID NO: SSDYYSPLRDLLLKS C*14:02 2056 SEQ ID NO: 14 TRPM2 HSKLQMHHVAQVLRE A*02:03 2057 SEQ ID NO: RLKSIFRRGLVKVAQ A*03:01 2058 SEQ ID NO: HPTMTAALISNKPEF A*11:01 2059 SEQ ID NO: LLGDFTQPLYPRPRH A*3303 2060 SEQ ID NO: ECGLMKKAALYFSDF B*15:01 2061 SEQ ID NO: VQLKEFYTWDTLLYL B*40:01 2062 SEQ ID NO: MKKAALYFSDFWNKL B*58:01 2063 SEQ ID NO:  HVTFTMDPIRDLLIW C*12:02 2064 SEQ ID NO: AALYFSDFWNKLDVG C*14:02 2065 SEQ ID NO: 15 IKZF3 SAAVLNDYSLTKSHE A*03:01 2066 SEQ ID NO: LERHVVSFDSSRPTS A*33:03 2067 SEQ ID NO: LNDYSLTKSHEMENV C*03:02 2068

To explore if somatic promoters might contribute to reducing tumor antigen burden and immunoreactivity in vivo, we proceeded to examine correlations between promoter alterations and intra-tumor T-cell activity in various primary GC cohorts. First, to detect promoter alterations in a cohort of 95 GC-normal pairs (SG cohort), we generated a customized Nanostring panel targeting the top 95 recurrent GC somatic promoters, measuring transcripts associated with either the canonical promoter or the alternative promoter. There was a significant correlation between the Nanostring data and RNA-seq (FIG. 16, r=0.65, P<0.001), with ˜35% of transcripts driven by alternate promoters upregulated in more than half of the GCs (FIG. 4D). Second, to examine markers of T-cell activity in these same GC samples, we analyzed previously published microarray data to measure CD8A (a measure of CD8+ tumor infiltrating lymphocytes), and granzyme A (GZMA) and perforin (PRF1), which are both T-cell effectors and validated markers of T-cell cytolytic activity. We confirmed that these three genes (CD8A, GZMA, and PRF1) were not themselves associated with somatic promoters. Comparing the top and bottom quartiles, GCs with high somatic promoter usage exhibited significantly lower GZMA and PRF1 levels (P<0.001 and P=0.01, Wilcoxon Test) indicating lower T-cell cytolytic activity (FIG. 4E, top left), and also a trend towards lower CD8A levels (P=0.14, Wilcoxon one sided test). Using two different algorithms (ASCAT and ESTIMATE), we further confirmed that the decreased GZMA and PRF1 levels are independent of tumor purity differences between GCs (FIG. 16). Similar results were obtained upon splitting the GC samples based on median promoter usage score (GZMA, P<0.001 and PRF1, P=0.03). Patients with GCs exhibiting high somatic promoter usage (top 25%) also showed poor survival compared to patients with GCs with low somatic promoter usage (bottom 25%) (FIG. 4e top right, HR 2.55, P=0.02). Again, dividing patients by their median somatic promoter usage score also showed similar survival differences (FIG. 11, HR=1.81, P=0.04).

To validate these findings, we then analyzed two other prominent GC cohorts—one from TCGA, and another from the Asian Cancer Research Group (ACRG). In the TCGA cohort, availability of RNA-seq data allowed us to infer somatic promoter usage directly from next-generation sequencing (NGS) data (FIG. 2c ). Similar to the Singapore cohort, TCGA GCs with high somatic promoter usage (top 25%) exhibited decreased CD8A (P=0.002, Wilcoxon one sided test), GZMA (P=0.001, Wilcoxon one sided test) and PRF1 levels (P=0.005, Wilcoxon one sided test, FIG. 4e bottom left) compared to GCs with low somatic promoter usage (bottom 25%) in a manner independent of tumor purity (FIG. 16). Notably, as previous studies have suggested that somatic mutation burden may also correlate with intra-tumor T-cell cytolytic response, we further repeated the analysis after adjusting for the total number of missense mutations in each sample using a regression based approach. Even after correcting for somatic mutation burden, we still observed decreased CD8A (P=0.02, Wilcoxon one sided test), GZMA (P=0.01, Wilcoxon one sided test) and PRF1 expression (P=0.03, Wilcoxon one sided test) in samples with high somatic promoter usage (top 25% against bottom 25%) (FIG. 11).

We leveraged a third independent cohort of GC samples from ACRG. Using NanoString to target 89 canonical and alternative promoters along with various immune markers, we profiled 264 primary GC samples from the ACRG cohort. 40% of alternative promoter transcripts showed tumor specific expression in more than half of the samples (FIG. 11). Once again, samples with high somatic promoter usage (top 25%) showed significantly lower expression of T-cell cytolytic activity markers including CD8A (P=0.035, Wilcoxon one sided test), CD4A (P=0.005, Wilcoxon one sided test), GZMA (P=0.001, Wilcoxon one sided test) and PRF1 (P=0.025, Wilcoxon one sided test) (FIG. 4e , bottom right) (FIG. 16). Similar results were obtained upon splitting the GC samples based on median promoter usage score (Table 11) Also, after adjusting for mutational burden (for cases where information is available), samples with high somatic promoter usage still showed decreased CD8A (P=0.167, Wilcoxon one sided test), GZMA (P=0.009, Wilcoxon one sided test), and PRF1 (P=0.03, Wilcoxon one sided test) expression (FIG. 11). Taken collectively, these results, observed across multiple GC cohorts and assessed using diverse technologies (microarray, RNA-seq, Nanostring) all support a significant association between somatic promoter usage and reduced tumor immunity levels. Importantly, the decreased levels of T-cell cytolytic activity associated with somatic promoter usage are likely independent of tumor purity and mutational load.

TABLE 11 P values of Wilcoxon test between ACRG samples with high and low somatic promoter usage. Top and Bottom Divided by median Immune Marker 25 pctl (50 pctl) CD4A 0.01151 0.06053 CD8A 0.07829 0.02482 CTLA4 0.2048 0.2952 FOXP3 0.1054 0.1673 GZMA 0.002593 0.005957 IFNg 0.2376 0.8045 IL-10 0.8391 0.9311 LAG3 0.1672 0.2627 PD1 0.1192 0.1506 PDL1 0.5668 0.5869 PRF1 0.01272 0.05873 TIM3 0.578 0.9424 TNFA 0.1394 0.7184 * All P values are from Wilcoxon two sided test

Somatic Promoter Associated Peptides are Immunogenic In Vitro

To functionally test the ability of N-terminal peptides depleted in GC to elicit immune responses, we conducted in-vitro assays using the high-throughput EPIMAX (EPItope MAXimum) platform, which allows multi-epitope testing for both T cell proliferation and cytokine production. First, we identified N terminal peptides predicted to exhibit high HLA-binding affinities across a pool of healthy PBMC (peripheral blood mononuclear cell) donors. Second, selecting 15 alternative promoter-associated peptides for testing, we generated peptide pools for each peptide (Tables 9 and 10, Methods), which were then used to stimulate PBMCs from 9 healthy donors. T cell proliferation and cytokine production levels were measured and benchmarked against control peptides (Table 12). Across all 135 exposures (15 peptides across 9 donors), we observed strong cytokine responses for 79 peptide pools (58%; FC-2 relative to Actin peptides) (FIG. 4g ) inducing complex Th1, Th2 and Th17 polarizations in a donor dependent fashion (FIG. 17).

TABLE 12 Cytokine Responses of N terminal Peptides Fold change of total cytokine response (normal- ized Analyte concentration (pg/ml) Total against Treat- GM- IFN- IL- IL- IL- IL- IL- IL- IL- IL- IL- analytes Actin Sample ment CSF g 2 3 4 7 9 10 13 15 17A sCD40L TNFa (pg/ml) control) Donor 1 DNAH3 99.39 228.45 89 6.35 2.12 0.085 7.32 24.91 228.24 0.925 1.88 4.47 264.89 958.03 2.89 Donor 1 DST 114.18 149.87 58.02 11.41 0.03 0.085 14.11 57.29 311.22 0.925 1.58 8.97 251.98 979.67 2.96 Donor 1 EPS8L1 153.07 351.34 100.97 11.8 0.03 0.085 28.88 33.71 431.94 0.925 0.02 6.17 434.22 1553.16 4.69 Donor 1 FRMD4B 55.53 121.17 76.42 10.54 0.03 1.43 16.77 36.13 198.37 0.925 0.93 3.76 186.12 708.13 2.14 Donor 1 LAMA3 67.29 152.66 99.6 4.83 1.72 0.085 9.11 25.85 264.85 0.925 0.02 2.8 506.25 1135.99 3.43 Donor 1 MET 54.4 93.08 96.36 6.27 0.03 0.085 5.52 25.85 179.02 0.925 0.02 3.76 606.67 1071.99 3.23 Donor 1 MIB2 97.14 201.48 94.37 5.92 0.03 0.085 18.62 27 381.6 0.925 0.67 1.81 684.34 1513.99 4.57 Donor 1 MRC2 52.57 63.61 53.15 5.58 0.03 0.085 3.32 37.5 184.11 0.925 0.76 1.81 290.69 694.14 2.09 Donor 1 NOS2 31.72 130.64 26.25 3.51 0.03 0.085 5.04 28.47 133.76 0.925 0.02 1.62 154.92 516.99 1.56 Donor 1 PLEC 107.71 393.6 96.29 14.5 10.68 0.085 27.93 59.1 413.41 0.925 0.02 7.78 337.55 1469.58 4.43 Donor 1 PLEKHG5 74.89 128.23 96.23 9.37 3.33 0.085 9.16 40.97 207.45 0.925 4.22 3.64 236.32 814.82 2.46 Donor 1 PTGDS 29.12 223.36 63.06 2.73 0.03 0.085 10.02 48.05 254.29 0.925 0.02 0.01 395.74 1027.44 3.10 Donor 1 RASA3 33.95 50.06 58.28 3.84 0.03 0.085 8.6 39.39 196.78 0.925 0.02 0.01 157.88 549.85 1.66 Donor 1 TRPM2 121.32 323.62 90.23 6.24 2.53 0.085 18.26 51.65 368.92 0.925 0.02 7.61 428.91 1420.32 4.29 Donor 1 IKZF3 9.53 59.94 23.36 0.94 0.03 0.085 1.22 42.98 76.06 0.925 0.02 0.01 48.83 263.93 0.80 Donor 1 Actin 19.75 147.18 34.21 1.46 0.03 0.085 1.22 10.1 14.2 0.925 0.02 0.78 101.44 331.40 1.00 Donor 2 DNAH3 279.27 1324.9 24 0.5 0.03 0.085 1.22 18.44 156.05 0.925 2.26 4.59 130.71 1942.98 28.04 Donor 2 DST 773.57 6732.16 46.6 2 0.03 0.085 1.22 23.76 370.78 0.925 2.56 3.88 257.33 8214.90 118.57 Donor 2 EPS8L1 427.99 1030.19 85.97 3.33 4.33 0.085 18.4 21.15 386.22 0.925 0.76 4.3 167.42 2151.07 31.05 Donor 2 FRMD4B 390.31 1070.19 94.99 3.93 10.28 1.27 1.22 19.9 415.04 0.925 0.02 5.24 159.4 2172.72 31.36 Donor 2 LAMA3 358.14 643.22 67.18 2.34 0.03 0.085 1.22 11.66 362.67 0.925 0.02 0.17 109.58 1557.24 22.48 Donor 2 MET 302.2 256.37 64.56 1.53 0.91 0.085 1.22 14.16 312.32 0.925 2.39 4.24 84.79 1045.70 15.09 Donor 2 MIB2 173.84 141.37 17.97 0.73 0.03 0.085 1.22 13.23 153.31 0.925 0.02 0.65 61.99 565.37 8.16 Donor 2 MRC2 1401.1 5545.58 205.47 5.98 6.32 0.085 13.83 14.06 889.87 0.925 6.68 4.59 531.62 8626.11 124.50 Donor 2 NOS2 342.89 462.07 83.01 2.88 10.88 2.29 15.36 21.57 288.7 0.925 5.91 3.82 89.68 1329.99 19.20 Donor 2 PLEC 280.02 357.65 74.41 2.44 0.03 0.085 19.79 24.07 343.1 0.925 5.46 2.49 83.91 1194.38 17.24 Donor 2 PLEKHG5 236.12 757.03 103.14 2.69 4.13 0.085 1.22 24.39 155.22 0.925 1.54 6.63 89.39 1382.51 19.95 Donor 2 PTGDS 142.7 621.5 33.17 1.39 0.03 0.17 1.22 13.75 63.73 0.925 2.39 4.83 57.06 942.87 13.61 Donor 2 RASA3 630.2 2755.29 67.63 0.98 4.53 0.085 15.24 36.44 363.46 0.925 0.02 3.28 281.27 4159.35 60.03 Donor 2 TRPM2 495.45 1211.48 60.61 2.96 0.03 0.085 2.44 5.29 542.44 0.925 0.02 3.28 143.48 2468.49 35.63 Donor 2 IKZF3 427.38 1705.57 71.33 1.36 0.03 0.085 21.04 43.4 419.93 0.925 0.02 4.77 116.74 2812.58 40.59 Donor 2 Actin 15.58 7.71 11.28 0.76 0.03 1.73 1.22 5.29 13.75 0.925 0.02 1.81 9.18 69.29 1.00 Donor 3 DNAH3 42.21 664.34 19.01 0.005 0.03 0.085 1.22 5.08 15.32 0.925 0.02 0.01 29.25 777.51 4.56 Donor 3 DST 100.36 273.74 14.76 0.005 0.03 0.085 1.22 27 58.89 0.925 7.41 1.17 63.68 549.28 3.22 Donor 3 EPS8L1 208.07 530.49 41.94 1.07 3.73 0.085 1.22 13.12 107.94 0.925 0.85 0.01 50.21 959.66 5.63 Donor 3 FRMD4B 143.55 211.78 47.51 0.73 0.03 0.085 1.22 17.71 91.8 0.925 0.02 1.11 53.79 570.26 3.35 Donor 3 LAMA3 100.19 509.46 23.21 1.08 0.03 0.085 1.22 36.97 34.67 0.925 1.19 0.01 50.95 759.99 4.46 Donor 3 MET 143.98 322.33 34.04 1.99 0.03 0.085 1.22 12.39 29.84 0.925 2.64 0.01 54.62 604.10 3.55 Donor 3 MIB2 113.31 127.71 16.28 0.05 0.03 0.085 1.22 9.27 39.67 0.925 0.02 0.01 39.41 347.99 2.04 Donor 3 MRC2 150.52 323.25 48.19 0.96 0.03 0.085 1.22 11.66 54.63 0.925 0.58 0.09 74.36 666.50 3.91 Donor 3 NOS2 186.72 328.5 75.34 4.54 0.03 0.085 1.22 18.02 95.19 0.925 1.96 2.06 69.18 783.77 4.60 Donor 3 PLEC 132.57 235.34 52.69 0.76 0.03 0.085 1.22 27.21 69.82 0.925 2.93 1.05 43.28 567.91 3.33 Donor 3 PLEKHG5 275.71 343.92 56.78 0.69 0.03 0.085 1.22 14.06 132.99 0.925 0.49 0.01 118.75 945.66 5.55 Donor 3 PTGDS 185.73 186.82 57.3 0.005 0.28 0.085 1.22 18.44 127.35 0.925 0.02 0.01 90.73 668.92 3.93 Donor 3 RASA3 133.59 93.84 40.44 0.01 0.06 0.085 1.22 9.68 73.67 0.925 2.3 1.49 53.69 411.00 2.41 Donor 3 TRPM2 176.42 154.05 46.74 1.05 0.03 1.43 1.22 10.93 133.4 0.925 0.02 0.01 72 598.23 3.51 Donor 3 IKZF3 32.69 169.24 18.82 0.005 0.03 0.085 1.22 10.52 16.55 0.925 0.02 0.01 21.41 271.53 1.59 Donor 3 Actin 56.66 60.86 13.4 0.56 4.53 0.085 1.22 2.56 5.96 0.925 2.89 0.01 20.69 170.35 1.00 Donor 4 DNAH3 0.66 0.005 2.21 0.005 0.03 0.085 1.22 0.41 0.58 0.925 0.02 0.01 2.38 8.54 1.24 Donor 4 DST 1.83 1.05 1.06 0.005 0.03 0.085 1.22 3.61 2.32 0.925 0.02 0.01 19.23 31.40 4.55 Donor 4 EPS8L1 0.66 1.35 0.98 0.005 0.03 2.01 1.22 4.24 1.95 0.925 0.02 0.01 1.86 15.26 2.21 Donor 4 FRMD4B 0.66 0.005 2.01 0.07 0.03 0.085 1.22 2.02 1.19 0.925 0.02 0.01 0.6 8.85 1.28 Donor 4 LAMA3 0.66 2.26 1.99 0.005 0.03 0.085 1.22 0.09 1.25 0.925 0.02 0.01 2.34 10.89 1.58 Donor 4 MET 0.66 0.3 1.19 0.005 0.03 0.085 1.22 4.77 2.69 0.925 0.13 0.01 1.61 13.63 1.98 Donor 4 MIB2 0.66 0.005 1.6 0.005 0.03 0.085 1.22 6.55 0.03 0.925 0.02 0.01 2.12 13.26 1.92 Donor 4 MRC2 0.66 1.05 0.98 0.005 0.03 0.085 1.22 4.77 0.3 0.925 0.02 0.01 2.08 12.14 1.76 Donor 4 NOS2 0.66 2.49 1.02 0.005 0.03 0.085 1.22 6.55 2.14 0.925 0.02 0.01 1.47 16.63 2.41 Donor 4 PLEC 1.42 0.005 1.66 0.005 0.03 0.085 1.22 5.29 0.79 0.925 0.31 0.02 16.87 28.63 4.15 Donor 4 PLEKHG5 0.66 0.005 1.15 0.005 0.03 0.085 1.22 3.19 1.19 0.925 0.02 0.01 0.8 9.29 1.35 Donor 4 PTGDS 0.66 3.65 2.26 0.005 0.03 0.085 1.22 3.19 2.08 0.925 0.02 0.01 10.06 24.20 3.51 Donor 4 RASA3 0.66 0.01 2.55 0.005 0.03 0.085 1.22 3.3 1.44 0.925 0.02 0.01 1.81 12.07 1.75 Donor 4 TRPM2 0.66 1.35 1.32 0.005 0.03 0.085 1.22 4.98 1.05 0.925 0.02 0.01 1.7 13.36 1.94 Donor 4 IKZF3 0.66 0.9 1.21 0.005 0.03 0.085 1.22 2.56 3.12 0.925 0.02 0.01 3.25 14.00 2.03 Donor 4 Actin 0.66 0.01 1.27 0.005 0.03 0.085 1.22 0.18 0.99 0.925 0.02 0.01 1.49 6.90 1.00 Donor 5 DNAH3 0.66 0.005 1.66 0.84 0.03 0.085 1.22 2.87 1.05 0.925 0.27 0.01 2.82 12.45 0.78 Donor 5 DST 0.66 0.6 0.79 0.005 0.03 0.085 1.22 3.61 3.18 0.925 0.02 0.01 2.06 13.20 0.82 Donor 5 EPS8L1 0.66 0.16 1.93 0.005 0.03 1.43 1.22 3.4 1.19 0.925 0.58 0.01 3.54 15.08 0.94 Donor 5 FRMD4B 0.66 2.03 1.71 0.005 0.03 0.085 1.22 0.09 0.3 0.925 0.02 0.01 1.86 8.95 0.56 Donor 5 LAMA3 0.66 0.01 1.93 0.005 0.03 2.29 1.22 0.41 0.3 0.925 0.02 0.01 1.86 9.87 0.62 Donor 5 MET 0.66 0.005 1.69 0.005 0.03 0.085 1.22 0.09 1.44 0.925 0.02 0.01 2.54 8.72 0.54 Donor 5 MIB2 0.66 0.005 2.44 0.005 0.03 0.95 1.22 1.71 0.06 0.925 0.02 0.01 2.71 10.75 0.67 Donor 5 MRC2 0.66 0.005 3.06 0.005 0.03 0.085 1.22 0.09 0.92 0.925 0.02 0.01 1.38 8.41 0.52 Donor 5 NOS2 0.66 1.2 1.9 0.005 0.03 0.085 1.22 0.09 1.89 0.925 1.11 0.01 3.63 12.76 0.80 Donor 5 PLEC 0.66 0.01 1.56 0.005 0.03 0.085 1.22 1.28 0.03 0.925 0.85 0.01 2.06 8.73 0.54 Donor 5 PLEKHG5 0.66 0.005 1.77 0.54 0.49 0.085 1.22 0.09 1.19 0.925 0.93 0.01 3.21 11.13 0.69 Donor 5 PTGDS 0.66 0.005 0.48 0.005 0.03 0.085 1.22 2.66 2.57 0.925 1.71 0.01 2.08 12.44 0.78 Donor 5 RASA3 0.66 0.3 2.21 0.005 0.03 0.085 1.22 1.49 1.44 0.925 0.02 0.01 1.9 10.30 0.64 Donor 5 TRPM2 0.66 0.005 1.1 0.005 0.03 0.085 1.22 0.09 0.03 0.925 0.02 0.01 0.92 5.10 0.32 Donor 5 IKZF3 0.66 4.81 2.52 0.005 0.03 2.94 1.22 4.66 0.03 0.925 0.02 0.01 1.52 19.35 1.21 Donor 5 Actin 0.66 1.65 1.4 0.005 0.03 0.085 1.22 5.5 1.44 0.925 0.02 0.01 3.08 16.03 1.00 Donor 6 DNAH3 59.45 150.57 19.71 0.58 0.91 1.73 1.22 26.38 150.33 0.925 28.58 5.59 367.48 813.46 3.66 Donor 6 DST 44.3 186.38 22.05 1.56 0.03 0.085 28.27 21.57 149.86 0.925 6.68 4.12 170.63 636.19 2.86 Donor 6 EPS8L1 47.7 132.54 24.08 2.42 0.03 0.085 1.22 23.24 53.62 0.925 10.24 4.59 322.88 623.57 2.81 Donor 6 FRMD4B 12.51 94.1 18.98 0.5 4.13 0.78 1.22 27 33.89 0.925 0.8 0.24 24.26 219.34 0.99 Donor 6 LAMA3 47.4 31 11.77 0.54 0.03 0.085 1.22 15 48.92 0.925 8.14 0.01 254.81 419.85 1.89 Donor 6 MET 36.59 255.47 19.03 1.92 0.03 0.4 1.22 59.85 64.07 0.925 3.14 4.24 56.57 503.46 2.27 Donor 6 MIB2 28.73 46.26 15.32 1.69 7.7 0.085 1.22 16.35 44.57 0.925 1.58 0.58 202.54 367.55 1.65 Donor 6 MRC2 30.56 173.28 11.42 0.3 0.03 0.085 1.22 15.31 25.45 0.925 13.84 2.86 70.54 345.82 1.56 Donor 6 NOS2 70.25 513.42 21.89 2.25 0.03 1.11 1.22 72.8 117.93 1.85 2.77 2.06 197.11 1004.69 4.52 Donor 6 PLEC 52.82 69.38 21.92 1.42 0.03 0.085 1.22 20.11 58.11 0.925 16.23 2.43 262.58 507.26 2.28 Donor 6 PLEKHG5 23.2 140.24 15.8 0.19 0.03 0.085 1.22 20.73 55.53 0.925 1.96 0.17 136.4 396.48 1.78 Donor 6 PTGDS 44.5 194.94 14.38 1.12 0.03 0.085 1.22 30.35 54.69 0.925 6.64 2.43 125.84 477.15 2.15 Donor 6 RASA3 67.6 91.21 19.34 1.53 0.03 0.085 7.62 43.82 212.13 0.925 14.56 2.18 273.27 734.30 3.31 Donor 6 TRPM2 24.72 145.01 12.57 0.005 0.03 0.085 1.22 22.4 16.66 0.925 1.5 3.28 67.52 295.93 1.33 Donor 6 IKZF3 63.92 108.75 23.63 1.97 0.03 0.085 5.1 46.57 131.23 0.925 22.4 2.86 116.65 524.12 2.36 Donor 6 Actin 18.81 135.48 11.03 0.5 0.03 0.085 1.22 4.66 8.77 0.925 2.22 0.01 38.39 222.13 1.00 Donor 7 DNAH3 25.1 28.72 2.1 0.005 0.03 0.085 1.22 7.49 2.45 0.925 0.02 0.09 48.76 117.00 1.64 Donor 7 DST 20.84 93.16 3.11 0.005 0.03 0.085 1.22 10.1 4.73 0.925 1.02 0.01 80.77 216.01 3.03 Donor 7 EPS8L1 1.32 0.9 2.84 0.005 0.03 0.085 1.22 3.4 0.03 0.925 0.63 0.01 7.74 19.14 0.27 Donor 7 FRMD4B 12.7 21.99 3.25 0.005 0.03 0.085 1.22 2.66 1.7 0.925 0.02 0.01 27.73 72.33 1.01 Donor 7 LAMA3 2.88 3.49 3.13 0.005 0.03 0.085 1.22 1.06 2.32 0.925 0.02 0.38 7.3 22.85 0.32 Donor 7 MET 0.66 1.05 1.82 0.005 0.03 0.085 1.22 3.09 0.22 0.925 0.02 0.01 8.53 17.67 0.25 Donor 7 MIB2 44.9 19.98 7.32 0.005 0.03 0.085 1.22 0.63 8.89 0.925 0.02 0.01 30.68 114.70 1.61 Donor 7 MR2C2 4.99 6.61 2.17 0.005 0.03 0.085 1.22 0.09 2.2 0.925 0.02 0.01 15.08 33.44 0.47 Donor 7 NOS2 64.4 61.11 9.55 0.38 0.03 2.29 1.22 3.93 10.2 0.925 0.18 0.01 29.13 183.36 2.57 Donor 7 PLEC 68.55 449.86 8.19 0.005 0.03 0.085 1.22 6.34 13.64 0.925 0.02 1.43 36.75 587.05 8.23 Donor 7 PLEKHG5 39.34 37.86 7.75 0.005 0.03 0.085 1.22 7.6 5.31 0.925 0.02 2.92 55.5 158.57 2.22 Donor 7 PTGDS 32.88 24.01 4.51 0.005 2.73 0.085 1.22 7.6 3.9 0.925 0.02 0.01 45.13 123.03 1.73 Donor 7 RASA3 42.8 44.03 7.54 0.005 0.03 0.085 1.22 7.8 14.2 0.925 0.02 0.31 36.75 155.72 2.18 Donor 7 TRPM2 29.69 140.85 2.97 0.005 0.03 0.085 1.22 25.75 3.72 0.925 0.02 0.01 124.46 329.74 4.62 Donor 7 IKZF3 43.4 29.69 8.26 0.005 0.03 0.085 1.22 5.71 6.88 0.925 0.02 0.45 37.8 134.48 1.89 Donor 7 Actin 3.31 6.53 0.77 0.01 0.03 2.29 1.22 7.7 0.14 0.925 0.02 0.01 48.35 71.31 1.00 Donor 8 DNAH3 110.13 191.67 72.91 1.32 0.03 4.85 3.47 9.27 105.51 0.925 0.4 0.78 121.93 623.20 47.79 Donor 8 DST 58.57 75.26 15.34 0.38 0.49 0.085 1.22 12.81 45.35 0.925 0.02 2.43 79.79 292.67 22.44 Donor 8 EPS8L1 88.89 63.7 41.38 1.19 0.03 0.085 6.26 10.1 121.32 0.925 0.02 4.24 92.38 430.52 33.02 Donor 8 FRMD4B 29.4 65.37 9.26 0.42 0.03 0.085 6.48 8.43 53.96 0.925 0.02 1.68 53.45 229.71 17.62 Donor 8 LAMA3 197.84 534.58 80.04 6.66 5.92 0.085 11.96 16.25 222.4 0.925 0.49 0.01 173.02 1250.18 95.87 Donor 8 MET 166.16 260.07 34.37 1.29 0.03 0.95 6.15 19.79 180.96 0.925 3.81 0.01 150.63 825.15 63.28 Donor 8 MIB2 55.58 97.75 8.09 3.34 0.03 0.4 10.38 14.37 48.48 0.925 4.22 0.01 70.89 314.47 24.12 Donor 8 MRC2 18.72 20.86 7.27 0.005 0.03 0.085 1.22 5.92 27.67 0.925 0.02 0.01 27.96 110.70 8.49 Donor 8 NOS2 79.04 62.03 23.6 1.36 0.03 0.085 8.21 11.98 120.62 0.925 1.28 0.01 53.5 362.67 27.81 Donor 8 PLEC 190.8 360.99 57.12 8.89 0.03 0.085 33.62 22.19 218.93 0.925 0.67 0.58 135.11 1029.94 78.98 Donor 8 PLEKHG5 30.37 80.65 6.89 0.005 0.03 0.085 1.22 12.39 12.62 0.925 0.08 0.01 34.21 179.94 13.76 Donor 8 PTGDS 17.08 7.78 5.28 0.005 1.92 0.085 1.22 13.44 25.12 0.925 0.67 2.31 25.09 100.93 7.74 Donor 8 RASA3 125.64 123.92 31.79 2.26 0.03 0.085 51.42 14.69 295.64 0.925 3.02 1.3 122.48 773.20 59.29 Donor 8 TRPM2 24.34 6.76 9.28 0.54 0.03 0.085 1.22 10.62 36.72 0.925 0.76 0.38 38.24 129.90 9.96 Donor 8 IKZF3 91.55 147.61 33.66 1.15 0.03 0.085 3.39 9.16 104.46 0.925 1.02 2.8 80.67 476.51 36.54 Donor 8 Actin 0.66 1.12 1.9 0.22 0.03 0.085 1.22 3.61 0.03 0.925 0.02 0.58 2.64 13.04 1.00 Donor 9 DNAH3 18.58 8.02 1.45 0.005 0.91 0.085 1.22 12.71 4.02 0.925 0.18 0.78 106.41 155.30 2.24 Donor 9 DST 18.02 15.32 3.89 0.17 0.03 0.085 1.22 8.22 1.19 0.925 0.02 0.01 64.97 114.07 1.64 Donor 9 EPS8L1 0.66 3.49 16.23 0.005 0.03 0.085 1.22 2.77 3.18 0.925 0.58 0.01 7.16 36.35 0.52 Donor 9 FRMD4B 5.93 3.18 2.93 0.005 0.03 0.085 1.22 0.09 0.92 0.925 0.04 0.01 12.73 28.10 0.40 Donor 9 LAMA3 0.66 4.03 2.75 0.005 0.03 2.01 1.22 1.28 1.51 0.925 0.02 0.01 6.68 21.13 0.30 Donor 9 MET 2.43 0.005 2.88 0.005 0.03 0.085 1.22 4.66 0.92 0.925 0.02 0.01 15.76 28.95 0.42 Donor 9 MIB2 13.91 10.55 5.42 0.005 0.03 0.085 1.22 6.55 4.25 0.925 0.02 0.01 63.45 106.43 1.53 Donor 9 MRC2 0.66 15.32 5.84 0.005 0.03 0.085 1.22 9.06 3.42 0.925 0.02 0.01 11.63 48.23 0.69 Donor 9 NOS2 27.96 18.69 4.86 0.005 0.03 0.085 1.22 22.19 2.01 0.925 1.19 0.01 220.43 299.61 4.32 Donor 9 PLEC 3.36 4.73 2.7 0.005 0.03 2.01 1.22 1.92 0.65 0.925 0.02 0.01 15.95 33.53 0.48 Donor 9 PLEKHG5 1.42 1.35 2.97 0.56 4.13 0.085 1.22 4.03 0.51 0.925 0.02 0.01 8.07 25.50 0.37 Donor 9 PTGDS 9.72 1.5 2.15 0.005 0.03 0.085 1.22 5.71 1.95 0.925 0.02 0.01 47.71 71.04 1.02 Donor 9 RASA3 2.48 6.14 2.12 0.005 0.03 0.085 1.22 4.03 0.03 0.925 1.19 0.01 14.78 33.05 0.48 Donor 9 TRPM2 5.56 0.9 4.77 0.38 0.03 0.085 1.22 4.03 1.32 0.925 0.02 0.01 10.04 29.29 0.42 Donor 9 IKZF3 9.67 0.005 6.18 0.005 0.03 1.43 1.22 5.08 1.32 0.925 0.08 0.01 31.98 57.94 0.83 Donor 9 Actin 0.66 3.49 0.77 0.36 0.03 2.01 1.22 2.13 1.05 0.925 0.58 0.01 56.18 69.42 1.00

To test the immunogenic capacity of specific N-terminal peptides in a more cellular setting, we then assessed responses of T cells previously primed to recognize either altered or wild-type peptides, when co-cultured with HLA-matched isogenic GC cells expressing either altered or wild-type peptides respectively (FIG. 12). By MHC-I affinity screening, a VMCDIFFSL nonamer in the WT RASA3 N-terminus was predicted to exhibit high MHC-I affinity binding for both the HLA-A02:01 (IC50=6.93 nm) and HLA-A02:06 (IC50=9.74 nm) alleles. Using HLA-A*02:06 T cells that are cross-reactive to HLA-A*02:01-positive AGS cells, we tested release of interferon gamma (IFNγ) from primed T cells after exposure to AGS lysates expressing either RASA3 CanT or SomT isoforms. ELISA assays demonstrated that T cells primed to recognize RASA3 CanT released significantly more IFNγ when co-cultured with RASA3 CanT-expressing AGS cells than when co-cultured with RASA3 SomT-expressing AGS cells. In contrast, T-cells primed with RASA3 SomT did not exhibit appreciable IFNγ release when co-cultured with RASA3 SomT expressing AGS cells, indicating that RASA3 SomT is less immunogenic (FIG. 12). Taken collectively, these in vitro results demonstrate that peptides predicted to be depleted in GCs through somatic promoter alterations can produce immunogenic responses, with the magnitude of immune responses depending on both peptide sequence and host immune background.

Somatic Promoters are Associated with EZH2 Occupancy

To identify potential oncogenic mechanisms driving somatic promoter alterations, we intersected the genomic locations of the somatic promoters with transcription factor binding sites (TFBS) of 237 transcription factors from 83 different tissues. Regions exhibiting somatic promoters were significantly enriched in regions associated with EZH2 (P<0.01) and SUZ12 (P<0.01) binding (FIG. 6a , Table 13), confirming earlier findings on a smaller cohort. Both EZH2 and SUZ12 are components of the PRC2 epigenetic regulator complex, which is upregulated in many cancer types including GC. To validate these findings, we then performed EZH2 Chip-sequencing on HFE-145 normal gastric epithelial cells (Methods and Materials). Concordant with the previous findings, we observed significant enrichment of EZH2 binding sites at somatic promoters compared to all promoters (Enrichment score 27 vs. 13 for all promoters, P<0.01), and this EZH2 enrichment remained significant when the gained somatic (Enrichment Score 28, P<0.01) and lost somatic promoters (Enrichment Score 24, P<0.01) were analyzed separately (FIG. 18).

TABLE 13 Somatic Promoters Overlapping EZH2/SUZ12 Binding Sites Annotation Loci Status Associated Gene chrX: 136647100- Known ZIC3 136648150 chr13: 100634350- Known ZIC2 100638150 chr13: 100630200- Known ZIC2 100634000 chr20: 50719850- Known ZFP64 50723350 chr18: 45660800- Known ZBTB7C 45664950 chr1: 185226150- Known Y_RNA 185227950 chr3: 13920600- Known WNT7A 13921250 chr2: 71126100- Known VAX2 71129800 chr5: 6448050- Known UBE2QL1 6451150 chr8: 72986650- Known TRPA1 72987850 chr22: 17082250- Known TPTEP1 17084550 chr19: 55657350- Known TNNT1 55658650 chr19: 55666950- Known TNNI3 55668450 chr22: 42320400- Known TNFRSF13C 42323750 chr8: 119962100- Known TNFRSF11B 119965650 chr21: 42873650- Known TMPRSS2 42881750 chr20: 1164650- Known TMEM74B 1168700 chr17: 53797250- Known TMEM100 53803100 chr11: 119291200- Known THY1 119294700 chr20: 55203450- Known TFAP2C 55206500 chr6: 10409250- Known TFAP2A; TFAP2A-AS1 10419650 chr6: 85471550- Known TBX18 85475350 chr20: 46411750- Known SULF2 46414250 chr8: 70403800- Known SULF1 70408450 chr5: 172753250- Known STC2 172757450 chr14: 38675750- Known SSTR1 38681750 chr7: 20824950- Known SP8 20827850 chr13: 95362100- Known SOX21; SOX21-AS1 95368650 chr3: 181428150- Known SOX2 181434750 chr8: 101660950- Known SNX31 101662650 chr20: 10197250- Known SNAP25; SNAP25-AS1 10201300 chr20: 48598400- Known SNAI1 48604100 chr14: 70346050- Known SMOC1 70347700 chr12: 85303950- Known SLC6A15 85307700 chr19: 17981100- Known SLC5A5 17986400 chr2: 228580350- Known SLC19A3 228583450 chr3: 121656650- Known SLC15A2 121658300 chr6: 100910100- Known SIM1 100913300 chr21: 44842150- Known SIK1 44848700 chr7: 37953600- Known SFRP4 37956950 chr4: 154708850- Known SFRP2 154714150 chr16: 23193600- Known SCNN1G 23197800 chr16: 23312800- Known SCNN1B 23315350 chr2: 200326950- Known SATB2 200329550 chr20: 50415800- Known SALL4 50419950 chr20: 981750- Known RSPO4 984100 chr1: 148247000- Known RP11-89F3.2 148248800 chr12: 54472600- Known RP11-834C11.6; RP11- 54477950 834C11.7 chr5: 72746300- Known RP11-79P5.7 72748200 chr1: 61103800- Known RP11-776H12.1 61106600 chr11: 134335600- Known RP11-627G23.1 134339750 chr11: 69830350- Known RP11-626H12.1 69834850 chr16: 89987550- Known RP11-566K11.4; TUBB3 89991500 chr16: 86319900- Known RP11-514D23.1 86321550 chr3: 50191700- Known RP11-493K19.3; SEMA3F 50195800 chr3: 132756350- Known RP11-469L4.1; TMEM108 132758550 chr6: 26613750- Known RP11-457M11.6 26615600 chr3: 87841650- Known RP11-451B8.1 87842700 chr1: 113391350- Known RP11-426L16.8; RP3- 113395900 522D1.1 chr12: 85711250- Known RP11-408B11.2 85713200 chr6: 106807450- Known RP11-404H14.1 106809950 chr1: 149230550- Known RP11-403I13.5 149232000 chr1: 222138950- Known RP11-400N13.2 222144050 chr3: 178577000- Known RP11-385J1.2 178578500 chr17: 46721450- Known RP11-357H14.17 46725800 chr5: 522450- Known RP11-310P5.2; SLC9A3 524750 chr15: 80542500- Known RP11-2E17.1 80545200 chr5: 74343750- Known RP11-229C3.2 74351250 chr5: 63460450- Known RNF180 63463050 chr1: 228742450- Known RNA5SP19 228743450 chr1: 228781900- Known RNA5S17; RNA5SP18 228785450 chr21: 38379100- Known RIPPLY3 38379750 chr21: 43180350- Known RIPK4 43189850 chr8: 104510350- Known RIMS2; RP11-1C8.4 104514700 chr10: 62758000- Known RHOBTB1 62762450 chr15: 90039550- Known RHCG 90040150 chr2: 86564650- Known REEP1 86566000 chr4: 82964050- Known RASGEF1B; RP11-689K5.3 82966400 chr3: 75707050- Known RARRES2P1 75708850 chr8: 85093500- Known RALYL 85097700 chr8: 128805200- Known PVT1 128810000 chr1: 29562850- Known PTPRU 29565950 chr7: 158378250- Known PTPRN2 158380350 chr1: 170630400- Known PRRX1; RP1-79C4.4 170636550 chr6: 150463250- Known PPP1R14C 150464400 chr12: 133264050- Known POLE; PXMP2; RP13- 133266950 672B3.2 chr5: 74990850- Known POC5 74992350 chr20: 56280450- Known PMEPA1 56287350 chr16: 57315850- Known PLLP 57319550 chr1: 6544500- Known PLEKHG5 6545600 chr14: 69950300- Known PLEKHD1 69951550 chr1: 201251800- Known PKP1 201254650 chr2: 42275400- Known PKDCC 42282950 chr12: 130823500- Known PIWIL1 130825600 chr4: 111557000- Known PITX2 111559350 chr7: 32107350- Known PDE1C 32111900 chr1: 55504650- Known PCSK9 55507550 chr15: 102029650- Known PCSK6 102031300 chr3: 142606500- Known PCOLCE2 142609050 chr14: 37129750- Known PAX9 37133800 chr1: 17443850- Known PADI2 17446850 chr8: 99951150- Known OSR2; RP11-44N12.5; STK3 99961750 chr1: 161991300- Known OLFML2B 161994850 chr7: 8473050- Known NXPH1 8474100 chr9: 87282200- Known NTRK2 87286150 chr19: 15309800- Known NOTCH3 15311950 chr4: 56500900- Known NMU 56504300 chr1: 183385400- Known NMNAT2 183388500 chr8: 41502400- Known NKX6-3 41510150 chr10: 134596450- Known NKX6-2; RP11-288G11.3 134599400 chr4: 85417400- Known NKX6-1 85421400 chr2: 233791350- Known NGEF 233792700 chrX: 107016000- Known NCBP2L; TSC22D3 107021000 chr11: 1150000- Known MUC5AC 1157350 chr7: 100607850- Known MUC12; MUC3A; RP11- 100613600 395B7.2 chr16: 56699800- Known MT1G; MT1H 56705700 chr12: 132313150- Known MMP17 132317650 chr7: 73036850- Known MLXIPL 73039200 chr19: 54482850- Known MIR935 54485950 chr9: 21554500- Known MIR31HG 21561150 chr17: 46800050- Known MIR3185; PRAC1; PRAC2 46802400 chr1: 1562700- Known MIB2 1565700 chr1: 205537050- Known MFSD4 205540700 chr13: 31480150- Known MEDAG 31483050 chr2: 132152200- Known MED15P3 132153000 chr3: 150959500- Known MED12L 150960300 chr2: 149894250- Known LYPD6B 149897500 chr11: 1889150- Known LSP1 1894600 chr1: 156896950- Known LRRC71 156898350 chr11: 61275250- Known LRRC10B; MIR4488 61276400 chr9: 103789900- Known LPPR1 103792650 chr16: 1013250- Known LMF1 1015550 chr1: 2980250- Known LINC00982; PRDM16 2991900 chr3: 75719150- Known LINC00960 75723200 chr20: 21085550- Known LINC00237 21087550 chr19: 55127750- Known LILRB1 55130550 chr7: 103968400- Known LHFPL3 103969950 chr1: 202182400- Known LGR6 202184350 chr1: 202161700- Known LGR6 202163400 chr1: 65991250- Known LEPR 65992850 chr1: 205424550- Known LEMD1; RP11-576D8.4 205426850 chr20: 9494050- Known LAMP5; RP5-1119D9.4 9498000 chr6: 129203450- Known LAMA2 129207800 chr19: 51485750- Known KLK7 51487700 chr3: 126073900- Known KLF15 126077300 chr1: 245315950- Known KIF26B 245321950 chr1: 180880350- Known KIAA1614 180883200 chr15: 81070500- Known KIAA1199 81075050 chr20: 43728950- Known KCNS1 43730250 chr14: 88788450- Known KCNK10 88791000 chr7: 119911950- Known KCND2 119914550 chr1: 111210100- Known KCNA3 111218300 chr16: 31366400- Known ITGAX 31369100 chr20: 13200350- Known ISM1 13202100 chr16: 54316250- Known IRX3 54322800 chr5: 2748900- Known IRX2 2751450 chr17: 38016450- Known IKZF3 38022250 chr22: 23229500- Known IGLC1; IGLJ1; IGLL5 23237350 chr19: 46579500- Known IGFL4 46581300 chr7: 45927300- Known IGFBP1 45929150 chr7: 23506000- Known IGF2BP3 23515500 chr6: 87646350- Known HTR1E 87648250 chr5: 175084150- Known HRH2 175086850 chr3: 11195250- Known HRH1 11198600 chr4: 175439400- Known HPGD 175445700 chr12: 54386800- Known HOXC6; HOXC9; HOXC- 54395700 AS1; HOXC-AS2 chr12: 54421700- Known HOXC6 54423400 chr12: 54410150- Known HOXC4; HOXC6; RP11- 54413050 834C11.14 chr12: 54446200- Known HOXC4 54449350 chr12: 54331500- Known HOXC13; HOXC-AS5 54334550 chr12: 54375250- Known HOXC10; HOXC-AS3; RP11- 54381900 834C11.12 chr17: 46701450- Known HOXB9 46705000 chr17: 46804450- Known HOXB13 46808100 chr7: 27159450- Known HOXA3; HOXA-AS2 27164850 chr7: 27208400- Known HOXA10; HOXA9; HOXA- 27220700 AS4; MIR196B; RP1- 170O19.20 chr7: 27221300- Known HOTTIP; HOXA11; HOXA11- 27251300 AS; HOXA13; RP1- 170O19.14 chr12: 54365950- Known HOTAIR; HOXC11 54373250 chr1: 6478800- Known HES2 6480950 chr11: 2016000- Known H19 2021350 chr11: 45942850- Known GYLTL1B 45946400 chr9: 140056700- Known GRIN1 140058300 chr15: 72488700- Known GRAMD2 72491050 chr17: 72425800- Known GPRC5C 72433550 chr5: 89854500- Known GPR98 89855350 chrX: 133117900- Known GPC3 133120700 chr19: 2700850- Known GNG7 2702900 chr7: 99526050- Known GJC3; RP4-604G5.1 99527900 chr8: 75230900- Known GDAP1; JPH1 75235150 chr7: 74379400- Known GATSL1 74380400 chr20: 61046800- Known GATA5; RP13-379O24.3 61052500 chr8: 11533800- Known GATA4 11540650 chr8: 11557150- Known GATA4 11568950 chr11: 11640700- Known GALNT18 11644650 chr12: 130645350- Known FZD10; FZD10-AS1 130646800 chr6: 96460900- Known FUT9 96466650 chr13: 39259850- Known FREM2 39263000 chr16: 86600550- Known FOXC2; RP11-463O9.5 86601800 chr6: 1608550- Known FOXC1 1611700 chr14: 38051900- Known FOXA1; TTC6 38070050 chr17: 39965500- Known FKBP10; LEPREL4 39970950 chr9: 133813800- Known FIBCD1 133816150 chr11: 69630950- Known FGF3 69635350 chr3: 13973700- Known FGD5P1 13975200 chr10: 95325600- Known FFAR4 95329150 chr7: 121942750- Known FEZF1; FEZF1-AS1 121947900 chr16: 86529000- Known FENDRR 86534050 chr21: 42687850- Known FAM3B 42691150 chr17: 66593700- Known FAM20A 66598900 chr1: 179711850- Known FAM163A 179712600 chr8: 53476650- Known FAM150A 53479500 chr4: 187025100- Known FAM149A 187028650 chr12: 124778800- Known FAM101A 124786100 chr7: 27281600- Known EVX1; EVX1-AS 27284150 chrX: 103498450- Known ESX1 103500200 chr1: 216892850- Known ESRRG 216898200 chr19: 55590850- Known EPS8L1 55593800 chr8: 144950100- Known EPPK1 144953650 chr17: 48608600- Known EPN3 48615100 chr1: 23037600- Known EPHB2 23041300 chr9: 112080500- Known EPB41L4B 112082950 chr7: 155250600- Known EN2 155253200 chr19: 14885900- Known EMR2 14888350 chr22: 37821950- Known ELFN2; RP1-63G5.5 37823900 chr19: 1286150- Known EFNA2; MUM1 1288700 chr20: 57874800- Known EDN3 57877300 chr15: 45399500- Known DUOX2; DUOXA2 45410700 chr16: 30021900- Known DOC2A 30023950 chr7: 96633500- Known DLX6; DLX6-AS1; DLX6-AS2 96636700 chr7: 96652750- Known DLX5 96654900 chr19: 6474700- Known DENND1C 6477300 chr10: 94831200- Known CYP26A1 94834300 chr4: 48987500- Known CWH43 48989500 chr8: 104382100- Known CTHRC1 104385900 chr5: 174177950- Known CTD-2532K18.1; MIR4634 174179050 chr14: 19924450- Known CTD-2314B22.3 19925600 chr14: 19640850- Known CTD-2314B22.1 19641750 chr15: 97838750- Known CTD-2147F2.1 97841300 chr5: 134912900- Known CTC-321K16.1; CXCL14 134915350 chr5: 134371700- Known CTC-276P9.1 134375750 chr16: 21288600- Known CRYM 21290700 chr2: 102002650- Known CREG2 102005250 chr15: 78632500- Known CRABP1 78634200 chr3: 9745600- Known CPNE9 9747050 chr16: 89640950- Known CPNE7 89643950 chr3: 99355450- Known COL8A1 99359900 chr6: 33160200- Known COL11A2 33161450 chr6: 35754500- Known CLPSL1 35755750 chr21: 36041150- Known CLIC6 36045150 chr17: 7161850- Known CLDN7; RP1-4G17.5 7167950 chr7: 73181100- Known CLDN3 73185850 chr3: 190034900- Known CLDN1; CLDN16 190041800 chr7: 29184550- Known CHN2; CPVL 29187650 chr2: 27340450- Known CGREF1 27342750 chr13: 28538700- Known CDX2 28543950 chr5: 149545100- Known CDX1 149550500 chr16: 68677900- Known CDH3; RP11-615I2.2 68681200 chr16: 68770300- Known CDH1 68774200 chr11: 6279800- Known CCKBR 6283200 chr18: 57363700- Known CCBE1; RP11-2N1.2 57365350 chr8: 76189900- Known CASC9 76191050 chr6: 17392850- Known CAP2 17396100 chr1: 20808950- Known CAMK2N1 20814450 chr7: 44265350- Known CAMK2B 44266400 chr8: 86350000- Known CA3 86351450 chr5: 2751850- Known C5orf38; IRX2 2754050 chr3: 138664900- Known C3orf72; FOXL2 138667100 chr17: 77019250- Known C1QTNF1; C1QTNF1-AS1 77024000 chr1: 223565950- Known C1orf65 223567600 chr1: 190440800- Known BRINP3; RP11- 190450200 161I10.1; RP11-547I7.2 chr2: 198650550- Known BOLL 198651850 chr15: 83952250- Known BNC1 83953300 chr4: 42152300- Known BEND4 42155900 chr17: 47209750- Known B4GALNT2 47211400 chr11: 134279600- Known B3GAT1 134282050 chr4: 94748600- Known ATOH1 94754050 chr9: 120175650- Known ASTN2 120177900 chr9: 133319400- Known ASS1 133324650 chr11: 2285750- Known ASCL2 2292550 chr16: 329250- Known ARHGDIG 332250 chr8: 145908800- Known ARHGAP39 145912600 chr4: 86395150- Known ARHGAP24 86399900 chr18: 24443050- Known AQP4; AQP4-AS1 24445900 chr11: 71318250- Known AP000867.1 71320050 chr5: 79864800- Known ANKRD34B 79866650 chr2: 133014850- Known ANKRD30BL; MIR663B 133015750 chr12: 85672750- Known ALX1 85675650 chr6: 168195400- Known AL009178.1; C6orf123 168198750 chr10: 4867450- Known AKR1E2 4870200 chr16: 3232300- Known AJ003147.8 3234150 chr8: 11203650- Known AF131216.5; TDH 11206800 chr17: 15847250- Known ADORA2B 15850800 chr7: 5601050- Known ACTB 5603800 chr7: 100490350- Known ACHE 100495550 chr3: 18734950- Known AC144521.1 18736300 chr2: 131593950- Known AC133785.1; ARHGEF4 131595800 chr4: 44447900- Known AC131951.1; KCTD8 44452050 chr17: 7982650- Known AC129492.6; ALOX12B 7984350 chr5: 1003400- Known AC116351.2; RP11- 1005850 43F13.4 chr2: 100721300- Known AC092667.2; AFF3 100722600 chr2: 286750- Known AC079779.4; FAM150B 288600 chr2: 132121200- Known AC073869.1 132122150 chr2: 233282700- Known AC068134.5; AC068134.6 233286450 chr16: 31495650- Known AC026471.6; SLC5A2 31500700 chr12: 54348250- Known AC012531.23; HOXC12 54351050 chr2: 118561200- Known AC009312.1 118562150 chr16: 51182700- Known AC009166.5; SALL1 51185700 chr2: 171671550- Known AC007405.8; GAD1 171676200 chr2: 66801200- Known AC007392.3 66811950 chr2: 71113350- Known AC007040.5 71116800 chr7: 15720950- Known AC005550.4; MEOX2 15728900 chr6: 1611750- Unknown — 1616000 chr15: 96958950- Unknown — 96961350 chr2: 66652100- Unknown — 66655200 chr2: 8833050- Unknown — 8834200 chr9: 17905350- Unknown — 17908250 chr5: 2746900- Unknown — 2748550 chr7: 45001800- Unknown — 45003250 chr12: 52257150- Unknown — 52258000 chr2: 218874000- Unknown — 218875450 chr19: 30214300- Unknown — 30216100 chr8: 140717350- Unknown — 140719650 chr7: 27264550- Unknown — 27266100 chr19: 48900250- Unknown — 48904400 chr16: 51186150- Unknown — 51187850 chr9: 132458700- Unknown — 132461300 chr11: 44337850- Unknown — 44339250 chr17: 46694850- Unknown — 46697150 chr10: 124898400- Unknown — 124900700 chr6: 10382900- Unknown — 10384750 chr8: 144489000- Unknown — 144490750 chr20: 49837550- Unknown — 49839250 chr3: 193921100- Unknown — 193922050 chr13: 100619800- Unknown — 100623100 chr1: 165320950- Unknown — 165322700 chr1: 180203650- Unknown — 180205650 chr1: 23543800- Unknown — 23544900 chr8: 144842350- Unknown — 144844000 chr5: 174162150- Unknown — 174163450 chr1: 184632450- Unknown — 184634700 chr13: 21295150- Unknown — 21296450 chr1: 156893100- Unknown — 156894550 chr20: 46434400- Unknown — 46435400 chr11: 33398050- Unknown — 33400750 chr6: 134216650- Unknown — 134218050 chr2: 45176050- Unknown — 45177700 chr13: 36044350- Unknown — 36045800 chr2: 45227500- Unknown — 45229600 chr10: 43427950- Unknown — 43429950 chr1: 152079200- Unknown — 152081300 chr7: 54731350- Unknown — 54733200 chr20: 4201500- Unknown — 4202700 chr8: 145555300- Unknown — 145556800 chr7: 64733800- Unknown — 64735500 chrX: 119124000- Unknown — 119127100 chr3: 14642850- Unknown — 14644150 chr10: 102488400- Unknown — 102492200 chr5: 42999400- Unknown — 43001150 chr21: 38063750- Unknown — 38066650 chr2: 131010400- Unknown — 131011600 chr19: 30018700- Unknown — 30020150 chr5: 72731550- Unknown — 72734700 chr8: 102092150- Unknown — 102094400 chr4: 4867350- Unknown — 4869600 chr4: 4854350- Unknown — 4855850 chr7: 156735150- Unknown — 156736500 chr1: 161442450- Unknown — 161443650 chr12: 54356450- Unknown — 54358100 chr1: 48174300- Unknown — 48176650 chr7: 25900700- Unknown — 25903050 chr10: 102830000- Unknown — 102833650 chr6: 137310350- Unknown — 137312150 chr1: 152081400- Unknown — 152084100 chr7: 27274550- Unknown — 27276500 chr12: 113904650- Unknown — 113906650 chr1: 17024500- Unknown — 17028900 chr5: 72528750- Unknown — 72529950 chr9: 99481850- Unknown — 99483650 chr1: 46954600- Unknown — 46956800 chr17: 26119900- Unknown — 26121850 chr1: 2253650- Unknown — 2254650 chr7: 73060250- Unknown — 73063150 chr19: 1754200- Unknown — 1758750 chr9: 29211200- Unknown — 29215700 chr7: 31375200- Unknown — 31377000 chr1: 165344500- Unknown — 165346650 chr10: 57389650- Unknown — 57391700 chr1: 163441550- Unknown — 163443100 chr1: 200842700- Unknown — 200844850 chr20: 44639000- Unknown — 44640950 chr2: 176952400- Unknown — 176953750 chr20: 6031700- Unknown — 6033850 chr5: 2738550- Unknown — 2740800 chr3: 74662150- Unknown — 74664400 chr10: 134600350- Unknown — 134602350 chr1: 152084900- Unknown — 152085650 chr8: 52520450- Unknown — 52521550 chr1: 121279850- Unknown — 121280850 chr13: 37729350- Unknown — 37731000 chr7: 8390700- Unknown — 8392150 chr12: 32818500- Unknown — 32820350 chr16: 15350450- Unknown — 15351950 chr2: 58342200- Unknown — 58346950 chr3: 112383300- Unknown — 112384750 chr19: 1682300- Unknown — 1683350 chr4: 27077050- Unknown — 27078000 chr8: 23507850- Unknown — 23509050 chr4: 10782250- Unknown — 10783600 chr17: 12927950- Unknown — 12928650 chr2: 11989300- Unknown — 11990550 chr7: 23074700- Unknown — 23076100 chr22: 28479200- Unknown — 28480250 chr9: 36763800- Unknown — 36766950 chr6: 28757250- Unknown — 28758600 chr1: 50032150- Unknown — 50033200 chr6: 4334150- Unknown — 4335300 chr1: 195732150- Unknown — 195733300 chr6: 170483200- Unknown — 170484200 chr12: 38447100- Unknown — 38448600 chr7: 86667750- Unknown — 86669950 chr16: 9683650- Unknown — 9684650 chr1: 171342100- Unknown — 171343300 chr20: 47203350- Unknown — 47204450 chr20: 62030950- Unknown — 62034000 chr1: 168323150- Unknown — 168325650 chr6: 10133900- Unknown — 10134950 chr4: 71924850- Unknown — 71926200 chrX: 130711450- Unknown — 130713600 chr12: 38549550- Unknown — 38551600 chr2: 131094200- Unknown — 131095000 chr1: 183626800- Unknown — 183628050 chr6: 28918100- Unknown — 28918850 chr2: 198504700- Unknown — 198507250 chr11: 71350450- Unknown — 71351500 chr20: 47001000- Unknown — 47003900 chr21: 10600500- Unknown — 10603150 chr3: 34131250- Unknown — 34132150 chr5: 7170200- Unknown — 7171750 chr17: 50486700- Unknown — 50487400 chr2: 122809550- Unknown — 122810150 chr8: 57178000- Unknown — 57179050 chr4: 142803450- Unknown — 142805000 chr10: 118367950- Unknown — 118370350 chrX: 115004100- Unknown — 115005700 chr3: 53961050- Unknown — 53963000 chr6: 28920750- Unknown — 28922800 chr17: 11769750- Unknown — 11770850 chr6: 1594950- Unknown — 1595600 chr15: 79783300- Unknown — 79784500 chr7: 83684250- Unknown — 83685650 chr18: 2246500- Unknown — 2247900 chr10: 36147250- Unknown — 36148500 chr7: 91023500- Unknown — 91025650 chr2: 79337900- Unknown — 79339650 chrX: 115002950- Unknown — 115003900 chr1: 34557900- Unknown — 34558600 chr19: 523250- Unknown — 524300 chr13: 91315500- Unknown — 91317200 chr6: 26330700- Unknown — 26333000 chr9: 115565950- Unknown — 115567400 chr14: 42380150- Unknown — 42381450 chr7: 76356350- Unknown — 76358750 chr13: 108578200- Unknown — 108579350 chr8: 90569800- Unknown — 90570900 chr3: 185842600- Unknown — 185844550 chr1: 207903150- Unknown — 207904800 chr2: 14988000- Unknown — 14988950 chr12: 47819700- Unknown — 47821500 chr1: 83728350- Unknown — 83730000 chr11: 105384700- Unknown — 105387850 chr3: 88557900- Unknown — 88558600 chr6: 142290050- Unknown — 142291600 chr3: 83265600- Unknown — 83268250

To experimentally test if inhibiting EZH2/PRC2 activity might modulate somatic promoter usage in GC, we treated IM95 GC cells with GSK126, a highly selective small-molecule inhibitor of EZH2 methyltransferase activity. This line was selected as it has previously shown to be sensitive to EZH2 depletion (FIG. 14). RNA-seq analysis of GSK126-treated IM95 cells at two treatment time points (Day 6 and 9) confirmed that genes upregulated upon EZH2 inhibition are enriched in previously identified PRC2 target gene sets (FIG. 18). GSK126 treatment caused deregulation of 2134 promoters in total. Of 1959 promoters exhibiting somatic alterations in primary GCs (FIG. 1D), GSK126 treatment caused deregulation of 251 somatic promoters in IM95 cells (12.8%). This proportion was significantly greater than the proportion of unaltered promoters exhibiting deregulation after GSK126 challenge (8.8%, OR 1.46 P<0.001, Fisher Test, FIG. 5B), suggesting heightened sensitivity of somatic promoters to EZH2 inhibition. The proportion of somatic promoters deregulated after EZH2 inhibition was also greater than the total proportion of genes (as defined by Gencode) regulated by GSK126 (1.5%, OR 9.21, P<0.001, FIG. 5B). Of those promoters exhibiting both GSK126 deregulation and also mapping to somatic promoters lost in primary GC, 89.6% were reactivated following GSK126 administration (78/87, FC>=2, qval <0.1, Methods and Materials), consistent with EZH2 functioning to repress these promoters. For example, FIGS. 5C and 5D highlights two lost somatic promoters (SLC9A9 and PSCA), exhibiting expression gain after GSK126 treatment (FIG. 5). These results thus suggest a general role for EZH2 in regulating epigenomic promoter alterations in GC.

Somatic Promoters Reveal Novel Cancer-Associated Transcripts

Finally, when analyzing the altered somatic promoters with respect to both proximity to known genes, we found that somatic promoters could be classified into annotated and unannotated categories. Annotated promoters were defined as promoters mapping close (<500 bp) to a known Gencode transcription start site (TSS), while unannotated promoters refer to those mapping to genomic regions devoid of known Gencode TSSs. The majority of promoters present in non-malignant tissues, and also promoters unchanged between tumors and normal tissues, mapped closely to previously annotated TSSs (72%-92%). In contrast, only 41% of promoters mapped to annotated promoter locations, while the remaining 59% mapped to “unannotated” locations, distant from Gencode TSSs and in many cases 2-10 kb away (FIG. 6a ).

To test the functional relevance of these unannotated promoters, we used GenoCanyon, a nucleotide level quantification of genomic functional potential that integrates multiple levels of conservation and epigenomic information. We observed that 81% of the unannotated promoter regions exhibited a maximum genome wide functional score of greater than 0.9 (range 0-1), indicating high functional potential. To ascertain tissue type specificities, we then applied tissue specific annotations using GenoSkyline, an extension of the GenoCanyon framework integrating Roadmap Epigenomics data We observed that GI tissues had the 3^(rd) highest median score after ESC and fetal tissues, consistent with our tumors being gastric in lineage and also de-differentiated (FIG. 5b ). In a separate analysis, recent studies have also suggested that endogenous repeat elements in the human genome may contribute significantly to regulatory element variation, and hypomethylation of repeat elements can induce cancer-associated transcription. We found that unannotated promoters, were also significantly enriched for the repeat elements ERV1 (P<0.0001 Unannotated vs. All) and L1 (P<0.0001 Unannotated vs. All, FIG. 13).

Compared to annotated promoters, unannotated promoters exhibited weaker H3K27ac signals suggesting that the former might have lower activity and decreased gene expression levels (FIG. 13). Supporting this, somatic promoters, even those supported by CAGE tags (indicating true promoters), exhibited significantly lower RNA-seq expression levels compared CAGE tag supported all promoters (FIG. 5c ). We thus hypothesized that unannotated promoters might be associated with low transcript levels, thereby rendering them more challenging to detect by conventional depth transcriptome sequencing given the very wide dynamic range of cellular transcriptomes (10-10,000 transcripts per cell for different genes) (FIG. 5d ). To test this possibility, we employed both down-sampling and up-sampling analysis. Not surprisingly, decreasing levels of RNA-seq depth caused a concomitant decrease in detected somatic promoter transcripts. For example, downsampling to −40M reads caused ˜250 transcripts (FPKM>0, FIG. 5e ) to be rendered undetectable at somatic promoters. More convincingly, in the reciprocal experiment, we experimentally generated deep RNA-seq data for matched 5 GC/normal pairs (average read depth 140M compared to standard 100M), and confirmed the additional detection of 435 new somatic promoter-associated transcripts (FPKM>0) (FIG. 5e ). We estimate that usage of deep RNA-sequencing data allowed us to discover additional transcripts for 22% of the unannotated promoters, not previously detectible at regular depth RNA-seq (FIG. 5f ). These results demonstrate that despite being associated with bona-fide cancer associated transcripts, many somatic promoters defined by epigenomic profiling may have been missed by conventional-depth RNA-seq.

Discussion

Identifying somatically-altered cis-regulatory elements, and understanding how these elements direct cancer-associated gene expression represents a critical scientific goal. Here, we defined close to 2000 promoters exhibiting altered activity in GC, indicating that somatic promoters in GC are pervasive. Promoters are canonically defined as proximal cis-regulatory elements that recruit general transcription factors to initiate transcription. However, selection and activation of TSSs by RNA polymerase at core promoters is dependent on multiple factors. Core promoters are differentially distributed between genes of different functions, and chromatin distributions and epigenetic landscapes of core promoter regions can also differ in a tissue specific manner. Presence of multiple transcription initiation sites within the same gene can generate distinct transcript isoforms with different 5′UTRs that can act as switches to regulate gene expression, and usage of alternative 5′UTRs can also impact both translation and protein stability of cancer associated genes such as BRCA1, TGF-β and ERG Such findings demonstrate that specific promoter element activity is complex and cell context dependent, with impact on downstream transcriptional, translational, and functional processes.

A significant proportion (˜18%) of somatic promoters corresponded to alternative promoters. In cancer, alternative promoter utilization is of major relevance, as increasing numbers of genes (e.g. LEF1, TP53, TGFB3) are now being shown to exhibit distinct alternative-promoter associated isoforms that differentially affect malignant growth. In the current study, we identified alternative promoters in genes both known and novel to GC biology with significant clinical and translational implications. For example, we discovered an alternative promoter at the EpCAM gene locus specifically activated in gastric tumors. In GC, EpCAM encodes a transmembrane glycoprotein which has been proposed as a marker for circulating tumor cells and EpCAM expression levels have been correlated with GC patient prognosis. However, little is known about the specific cellular mechanisms driving high EpCAM expression in GC. Our finding that EpCAM is regulated in GC not through its canonical promoter, but instead through a cancer-specific alternative promoter may lend credence to recent reports suggesting that in addition to acting as an experimentally convenient surface marker, EpCAM may actually play a more direct pro-oncogenic role in stimulating cellular proliferation.

Another novel example of an alternative promoter-associated gene, identified for the first time in our study, was RASA3. While a functional role for RASA3 in cancer remains to definitely established, studies from other biological fields have shown that RASA3 can inhibit RAP1, which in turn has been implicated in invasion and metastasis in various cancers. RASA3 depletion can enhance signaling by integrins and mitogen-activated protein kinases, and the possibility that RASA3 can act as tumor suppressor has also been recently suggested through independent cross-species cancer studies. A plausible role for RASA3 as a potential tumor suppressor is consistent with our own results where expression of wild-type RASA3 potently inhibited cell migration and invasion in GC cell lines, while N-terminal variant RASA3 enhanced migration and invasion in normal gastric epithelial cells. A third example of an alternative-promoter driven genes was MET, which has been extensively investigated as a target for cancer therapy. While we and others have previously reported expression of an N-terminal truncated MET variant in cancer, functional implications of this truncated MET variant have remained unclear. In the present study, experimental assessment of MET wild-type and variant signaling revealed that truncated MET variants may have different downstream signaling effects compared to full-length MET isoforms. Under the experimental conditions used, we observed significant differences in phosphorylation patterns of ERK, STAT3 and GAB1, in a manner consistent with MET-Var being more pro-oncogenic compared to MET-Var, as both ERK, STAT3, and GAB1 have been shown to facilitate MET-induced signaling. The MET signaling pathway is known to be particularly complex with multiple feedback loops, and understanding how expression of the N terminal short MET isoform might modulate downstream survival signaling will be an important subject of future research, particularly in light of recent clinical trials targeting MET in lung cancer using antibodies which have been unsuccessful.

Our study also revealed an unexpected relationship between somatic promoters and tumor immunity. Specifically, we discovered that alternative promoter isoforms overexpressed in GC were significantly depleted of N-terminal peptides predicted to be potentially immunogenic, based on computational predictions of high-affinity MHC Class I binding and other immunological assays. We believe that finding is relevant to cancer immunity, as it builds on previous findings from the literature establishing the existence of self-reactive T-cells, the potential immunogenicity of overexpressed tumor antigens, and the process of tumor immunoediting. First, while the majority of self-reactive T-cells are clonally deleted during early development, numerous groups have also demonstrated the frequent persistence of self-reactive T cells in the periphery. For example, analysis of transgenic mice has shown that 25-40% of autoreactive T cells are likely to escape clonal deletion even in the presence of the deleting ligand, and in humans, Yu et al has demonstrated that clonal deletion prunes the T-cell repertoire but does not fully eliminate self-reactive T-cell clones. Importantly, while such self-reactive T-cells are typically low-avidity and are not capable of recognizing self-antigens under normal physiological conditions, they still retain the ability to become activated and to produce effector and memory cells under conditions of appropriate stimulation, such as infection and the mounting of anti-tumor responses.

Second, in cancer, several studies have shown that self-reactive T-cells can exhibit immunologic activity towards overexpressed tumor antigens, even if these antigens are also expressed at lower levels in normal tissues. One well-known example is the melanocyte differentiation antigen Melan-A/MART-1, which is expressed by both normal melanocytes and overexpressed in malignant melanoma cells. T-cell recognition of Melan-A/MART-1 has been detected in 50% of melanoma patients, and even healthy individuals have been shown to exhibit a disproportionately high frequency of Melan-A/MART-1-specific T cells in the peripheral blood. Besides Melan-A/MART-1, other examples of tumor associated self-antigens inducing immunological recognition in both healthy individuals and cancer patients include tyrosinase-related proteins (TRP-1 and TRP-2) and glycoprotein (gp) 100 in melanoma, and HA in mastocytoma cells. Such examples clearly demonstrate that in certain cases, normally expressed proteins can still become immunogenic when overexpressed in cancer. Third, tumor immunoediting—the acquired capacity of developing tumors to escape immune control, is a recognized hallmark of cancer. Tumor immune escape can occur via different mechanisms, such as through upregulation of immune checkpoint inhibitors (eg PD-L1), and altered transcription of antigen presenting genes or tumor-specific antigens. For example, decreased expression of melanoma antigens (eg gp100, MART-1, and HA) has been associated with melanoma progression to later disease stages. Besides overt downregulation of the entire gene, it is thus highly plausible that transcriptional changes affecting splice forms and promoter variants may also contribute to tumor immunoediting. For example, very recent work in B-cell acute lymphoblastic leukemia (B-ALL) has described the production of N-terminally truncated CD19 transcript variants in response to CD19 CART (chimeric antigen receptor-armed T cells) therapy, clearly showing that promoter transcript variants can indeed arise as a consequence of immunologic pressure. Taken collectively, we believe that these previously established findings all point to a plausible role for alternative promoters in reducing the immunogenic potential of tumors. In this regard, our observation that regions exhibiting somatic promoter alterations showed a significant overlap with binding targets of the Polycomb repressive complex 2 (PRC2) epigenetic regulator complex, and are particularly sensitive to EZH2 inhibition, suggests that pharmacologic approaches for reawakening somatic promoter-associated epitopes might represent an attractive strategy for increasing anti-tumor T-cell immunoreactivity and anti-tumor activity.

In conclusion, our study indicates an important role for somatic somatic promoters in GC. We also note that a significant portion (52%) of the somatic promoters localized to unannotated TSSs, consistent with recent studies indicating the existence of hundreds of transcript loci remaining to be annotated. Interestingly, a large portion of the human transcriptome has been shown to originate from repetitive elements that can exhibit promoter activity and/or express noncoding RNAs. Unannotated promoters activated in our GC study were found to be enriched in ERV-1 and L1 repeat elements which have been shown to be associated with stage specific transcription in early human embryonic cells, suggesting a yet unknown functional role for these promoters. Analysis of these unannotated promoters is likely to provide fertile ground for new and hitherto unanticipated insights into mechanisms of GC development and progression. 

1. A method for determining the presence or absence of at least one promoter in a cancerous biological sample relative to a non-cancerous biological sample, comprising: contacting the cancerous biological sample with at least one antibody specific for histone modifications H3K4me3 and H3K4me1; isolating nucleic acid from the cancerous biological sample having a signal ratio of H3K4me3 relative to H3K4me1 greater than 1, wherein the isolated nucleic acid comprises at least one region specific to said histone modifications; detecting a signal intensity of H3K4me3 in the isolated nucleic acid; and determining the presence or absence of at least one promoter in the cancerous biological sample based on the change in the signal intensity of H3K4me3 relative to the signal intensity of H3K4me3 in a non-cancerous biological sample.
 2. The method of claim 1, wherein the cancerous and non-cancerous biological sample comprises a single cell, multiple cells, fragments of cells, body fluid or tissue.
 3. The method of any one of claims 1-2, wherein the cancerous and non-cancerous biological sample is obtained from the same subject.
 4. The method of any one of claims 1-3, wherein the cancerous and non-cancerous biological sample are each obtained from different subjects.
 5. The method of any one of claims 1-4, wherein the contacting step comprises the immunoprecipitation of chromatin with the antibodies specific for the histone modifications.
 6. The method of any one of claims 1-5, further comprising mapping at least one promoter from the cancerous biological sample against at least one reference nucleic acid sequence to identify a gene transcript associated with the at least one promoter.
 7. The method of claim 6, wherein the at least one reference nucleic acid sequence comprises a nucleic acid sequence derived from: i) an annotated genome sequence; ii) a de novo transcriptome assembly; and/or a non-cancerous nucleic acid sequence library or database.
 8. The method of claim 1, wherein the change of signal intensity of H3K4me3 is greater than a 1.5 fold increase or decrease relative to the signal intensity of H3K4me3 in the non-cancerous biological sample.
 9. The method of claim 8, wherein a change of signal intensity of H3K4me3 greater than a 1.5 fold increase relative to the signal intensity of H3K4me3 in a non-cancerous biological sample, correlates to the presence of at least one cancer-associated promoter in the cancerous biological sample.
 10. The method of claim 9, wherein the activity of the at least one cancer-associated promoter correlates with an increase of SUZ12 or EZH2 binding sites relative to the total promoter population.
 11. The method of claim 10, wherein the increase of SUZ12 or EZH2 binding sites correlates with an upregulation of activity of the at least one cancer-associated promoter.
 12. The method of claim 10, wherein the increase of SUZ12 or EZH2 binding sites correlates with a downregulation of activity of the at least one cancer-associated promoter.
 13. The method of any one of claims 1-12, wherein the at least one promoter is a canonical promoter that is positioned within 500 bp from a known gene transcript start site.
 14. The method of claim 13, wherein the gene transcript start site is associated with one or more of a cell-type specification gene, a cell adhesion gene, a cell mediated immunity gene, a gastric cancer-associated or deregulated gene, a PRC2 target gene or a transcription factor.
 15. The method of claim 14, wherein the gene transcript start site is associated with an oncogene.
 16. The method of claim 13, wherein the gene transcript start site is associated with a gene selected from the group consisting of MYC, MET, CEACAM6, CIDN7, CIDN3, HOTAIR, PVT1, HNF4α, RASA3, GRIN2D, EpCAM and a combination thereof.
 17. The method of any of claims 1-16, wherein the cancer is gastric cancer or colon cancer.
 18. The method of any of claims 1-17, wherein the at least one promoter is an alternative promoter that is associated with a canonical promoter, wherein the canonical promoter is present in both the cancerous biological sample and the non-cancerous biological sample, and wherein the alternative promoter is only present in the cancerous biological sample, or wherein the alternative promoter is only absent in the cancerous biological sample.
 19. The method of any of claims 1-12, wherein the at least one promoter is an unannotated promoter that is positioned more than 500 bp away from a gene transcript start site.
 20. The method of claim 18, further comprising: measuring the expression level of the at least one alternative promoter in the cancerous biological sample and non-cancerous biological sample, wherein the measuring comprises digital profiling of reporter probes; and determining the differential expression level of the at least one alternative promoter relative to the non-cancerous biological sample, based on the digital profiling of the reporter probes, to validate the presence or absence of at least one alternative promoter in the cancerous biological sample relative to a non-cancerous biological sample.
 21. The method of claim 20, wherein said step of measuring is conducted using a NanoString™ platform.
 22. A method for determining the prognosis of cancer in a subject, comprising, contacting a cancerous biological sample obtained from the subject with at least one antibody specific for histone modification H3K4me3 and H3K4me1; isolating nucleic acid from the cancerous biological sample having a signal ratio of H3K4me3 relative to H3K4me1 greater than 1, wherein the isolated nucleic acid comprises at least one region specific to said histone modifications; detecting a signal intensity of H3K4me3 in the isolated nucleic acid; and determining the presence or absence of at least one cancer-associated promoter in the cancerous biological sample based on the change in the signal intensity of H3K4me3 relative to the signal intensity of H3K4me3 in a reference nucleic acid sequence, wherein the presence or absence of the at least one cancer-associated promoter in the cancerous biological sample is indicative of the prognosis of the cancer in the subject.
 23. The method of claim 22, wherein the at least one cancer-associated promoter is an alternative promoter that is associated with a canonical promoter, wherein the canonical promoter is present in both the cancerous biological sample and the reference nucleic acid sequence, and wherein the alternative promoter is only present in the cancerous biological sample or wherein the alternative promoter is only absent in the cancerous biological sample.
 24. The method of claim 23, wherein the presence or absence of the at least one alternative promoter in the cancerous sample is indicative of a poor prognosis of cancer survival in the subject.
 25. The method of claim 23, further comprising: measuring the expression level of the at least one alternative promoter in the cancerous biological sample and the reference nucleic acid sequence, wherein the measuring comprises digital profiling of reporter probes; and determining the differential expression level of the at least one alternative promoter relative to the non-cancerous biological sample, based on the digital profiling of the reporter probes, to validate the presence or absence of at least one alternative promoter in the cancerous biological sample relative to the reference nucleic acid sequence.
 26. The method of claim 25, wherein said step of measuring is conducted using a NanoString™ platform.
 27. A biomarker for detecting cancer in a subject, the biomarker comprising at least one promoter having a change in signal intensity of H3K4me3 in a cancerous biological sample relative to a non-cancerous biological sample.
 28. The biomarker of claim 27, wherein the at least one promoter comprises an increase of EZH2 binding sites relative to the total promoter population.
 29. The biomarker of claim 27, wherein the at least one promoter is hypomethylated.
 30. The biomarker of claim 27, wherein the at least one promoter is hypermethylated.
 31. The biomarker of claim 27, wherein the at least one promoter is a canonical promoter that is positioned less than 500 bp away from a gene transcript start site.
 32. The biomarker of claim 31, wherein the gene transcript start site is associated with one or more of a cell-type specification gene, a cell adhesion gene, a cell mediated immunity gene, a gastric cancer-associated or deregulated gene, a PRC2 target gene or a transcription factor.
 33. The biomarker of claim 31, wherein the gene transcript start site is associated with an oncogene.
 34. The biomarker of claim 31, wherein the gene transcript start site is associated with a gene selected from the group consisting of MYC, MET, CEACAM6, CIDN7, CIDN3, HOTAIR, PVT1, HNF4α, RASA3, GRIN2D, EpCAM and a combination thereof.
 35. The biomarker of claim 27, wherein the at least one promoter is an alternative promoter that is associated with a canonical promoter, wherein the canonical promoter is present in both a cancerous sample and a non-cancerous sample, and wherein the alternative promoter is only present in a cancerous sample, or wherein the alternative promoter is only absent in a cancerous sample.
 36. The biomarker of claim 27, wherein the at least one promoter is an unannotated promoter that is positioned more than 500 bp away from a gene transcript start site.
 37. A method for modulating the activity of at least one cancer-associated promoter in a cell, comprising administering an inhibitor of EZH2 to the cell.
 38. A method for modulating the immune response of a subject to cancer, comprising administering to the subject an inhibitor of EZH2, wherein the EZH2 is associated with at least one cancer-associated promoter in the subject.
 39. The method of claim 38, wherein the inhibitor of EZH2 modulates the expression of immunogenic N-terminal peptides.
 40. The method of claim 38 or 39, wherein the at least one cancer-associated promoter is an alternative promoter that is associated with a canonical promoter, wherein the canonical promoter is present in both a cancerous sample and a non-cancerous sample, and wherein the alternative promoter is only present in a cancerous sample, or wherein the alternative promoter is only absent in a cancerous sample.
 41. The method of claim 40, wherein the alternative promoter is associated with a transcript variant, and wherein the transcript variant encodes a N-terminal protein variant.
 42. The method of claim 41, wherein the N-terminal protein variant is an N-terminal truncated protein or an N-terminal elongated protein.
 43. The method of any one of claims 38 to 42, wherein the inhibitor of EZH2 is a siRNA or a small molecule.
 44. The method of any one of claims 38 to 43, wherein the inhibitor of EZH2 is GSK126.
 45. A method for determining the presence or absence of at least one cancer-associated promoter in a cancerous biological sample relative to a non-cancerous biological sample, comprising: contacting the cancerous biological sample with at least one antibody specific for histone modifications H3K4me3 and H3K4me1; isolating nucleic acid from the cancerous biological sample having a signal ratio of H3K4me3 relative to H3K4me1 greater than 1, wherein the isolated nucleic acid comprises at least one region specific to said histone modifications; detecting a signal intensity of H3K4me3 in the isolated nucleic acid at a read depth of 20M; and determining the presence or absence of at least one cancer-associated promoter in the cancerous biological sample based on the change in the signal intensity of H3K4me3 relative to the signal intensity of H3K4me3 in a non-cancerous biological sample.
 46. An inhibitor of EZH2 for use in modulating the activity of at least one cancer-associated promoter in a cell.
 47. Use of an inhibitor of EZH2 in the manufacture of a medicament for modulating the activity of at least one cancer-associated promoter in a cell.
 48. An inhibitor of EZH2 for use in modulating the immune response of a subject to cancer, wherein the EZH2 is associated with at least one cancer-associated promoter in the subject.
 49. Use of an inhibitor of EZH2 in the manufacture of a medicament for modulating the immune response of a subject to cancer, wherein the EZH2 is associated with at least one cancer-associated promoter in the subject. 